CurrentCentenePolicy N/A

V1.2025 Concert Genetic Testing: Prenatal Diagnosis (via Amniocentesis, CVS, or PUBS) and Pregnancy Loss

Defines medical necessity criteria for genetic testing methods (CMA, conventional karyotype, targeted panels, exome, genome) performed on fetal samples via amniocentesis, CVS, PUBS and on products of conception (POC) for prenatal diagnosis and evaluation of pregnancy loss.

Policy Summary

PayerCentene

PolicyV1.2025 Concert Genetic Testing: Prenatal Diagnosis (via Amniocentesis, CVS, or PUBS) and Pregnancy Loss

Policy CodePolicy N/A

Change TypeRevisions, coding updates, criteria clarifications

Effective DateN/A

Next Review DateN/A

Key ActionDocument that the member has received counseling regarding benefits and limitations of the relevant prenatal or pregnancy-loss genetic testing and obtain prior authorization per Centene plan procedures.

SourceLink

POLICY UPDATE CHANGES

Added PLA code 0496U to CMA prenatal criteria to match policy reference table and added new PLA test to Policy Reference Table.

Updated CMA for pregnancy loss counseling requirements and replaced 'after' with 'at or greater than' regarding gestational age.

Expanded and clarified criteria for Noonan spectrum disorders: lowered nuchal translucency threshold to 3.0 mm when additional findings are present and included panels/codes.

Moved prenatal diagnosis for single-gene disorders criteria to General policy and added multiple single-gene and panel CPT codes to the policy reference table.

Removed one criterion regarding exome or genome sequencing for pregnancy loss on products of conception due to lack of volume in claims.

Minor rewording for clarity throughout the policy and reformatted reference tables/background for genome sequencing.

Added PLA code 0496U to the Chromosomal Microarray Analysis (CMA) criteria set.

Prenatal Diagnosis for Single Gene Disorders criteria moved to the General policy.

Removed out of date reference and added new reference in Prenatal Diagnosis via Exome Sequencing.

3Major test categories (CMA, Karyotype, Sequencing)

2POC indications listed (recurrent loss, >=20 weeks)

1PLA codes added

1Criterion removed (exome/genome for POC)

MultipleNumber of CPT code groups referenced

Coverage Summary

This policy defines medical necessity criteria for genetic testing performed on fetal samples obtained via amniocentesis, chorionic villus sampling (CVS), or percutaneous umbilical cord blood sampling (PUBS), and for testing of products of conception (POC)chromosomal microarray analysis (CMA), conventional karyotype, targeted panels (e.g., Noonan/RASopathy, skeletal dysplasia), and exome sequencing under specified indications. The policy states that genome sequencing is investigational for prenatal diagnosis. CMA is preferred as the primary test when fetal major structural abnormalities are identified on ultrasound and is supported for POC evaluation in cases of intrauterine fetal demise/stillbirth or recurrent pregnancy loss. Exome sequencing is supported when karyotype/CMA are normal and specific severe fetal findings are present (e.g., non-immune hydrops fetalis or two or more major malformations affecting different organ systems).

Administrative updates in the most recent revisions include addition of a PLA code (0496U) to the CMA criteria set and wording changes to pregnancy-loss indications (e.g., inclusion of “history of recurrent pregnancy loss” and use of “at or greater than 20 weeks” gestational age). Single-gene prenatal criteria were relocated to the General policy; genome sequencing remains classified as investigational.

Quick facts / thresholds

Nuchal translucency threshold (high)>= 5.0 mm

Nuchal translucency threshold (lower + additional findings)>= 3.0 mm with specified additional ultrasound findings

POC gestational age threshold>= 20 weeks (IUFD/stillbirth)

Recurrent pregnancy loss definition2 or more failed clinical pregnancies

PLA codes added1 (0496U)

Overall coverage stancemixed

Medical Necessity Criteria (grouped by test and indication)

Chromosomal Microarray Analysis (CMA) for Prenatal Diagnosis

Chromosome microarray analysis (81228, 81229, 81265, 88235, 0469U) for prenatal diagnosis via amniocentesis, CVS, or PUBS may be considered medically necessary when:

ALL of the following

Member/enrollee has received counseling regarding the benefits and limitations of prenatal screening and diagnostic testing (including chromosome microarray via amniocentesis, CVS or PUBS) for fetal chromosome abnormalities.

Chromosomal Microarray Analysis (CMA) for Prenatal Diagnosis - Investigational

Investigational when:

ANY of the following

All other indications not meeting the medical necessity criteria above.

Coding Reference (grouped by status)

CMA common CPT codes (prenatal and pregnancy loss)CPTCovered

81228
81229
81265
88235
0469U
0496U	PLA code added to criteria set (mentioned in revisions)

Conventional karyotype CPT codes (prenatal and POC)CPTCovered

88235
88261
88262
88263
88264
88267
88269
88280
88291

Noonan/RASopathy panel CPT codesCPTCovered

81404
81405
81406
81407
81479
81442

Skeletal dysplasia panel CPT codesCPTCovered

81404
81405
81408
81479
81265
88235

Exome sequencing CPT codesCPTCovered

81415
81416
81265
88235

Genome sequencing CPT codesCPTExperimental

81425
81426
81427
0335U
0336U

Additional CPT codes added in revisions (single-gene and panels)CPT

0218U
81178
81179
81180
81181
81182
81183
81184
81185
81186

1–10 of 36

1/4

PLA code added to CMA criteria setNDC|mixedCovered

0496U

PLA code added to Chromosomal Microarray Analysis (CMA) criteria set

Provider Actions & Billing Impact

Documentation Required

Pretest counseling documentation

Documentation that the member/enrollee has received counseling regarding the benefits and limitations of the relevant prenatal or pregnancy-loss genetic testing is required for medical necessity determination. Counseling should address the benefits and limitations of screening and diagnostic options (including CMA, karyotype, exome sequencing where applicable) and be documented in the medical record prior to testing.

Document that pretest counseling was provided and topics discussed (benefits, limitations, alternatives).
For pregnancy loss (POC) testing, document counseling specific to CMA on products of conception when applicable.
Include counseling notes in chart or attach counseling summary when submitting for medical necessity review.

Prior Authorization

Prior authorization likely required per payer

Background & Evidence

The policy aligns with guidance from major professional bodies (ACOG, SMFM, ACMG, ASRM). Consistent with ACOG/SMFM guidance, CMA is recommended as the primary test for prenatal diagnosis when one or more fetal structural abnormalities are identified on ultrasound and is recommended as preferred testing for evaluation of intrauterine fetal death or stillbirth where cytogenetic analysis is desired. The policy references ACMG points-to-consider that exome sequencing may be considered when CMA and karyotype are non-diagnostic and there are ultrasound anomalies, and cites meta-analysis evidence supporting high diagnostic yield of ES in non-immune hydrops fetalis. ACOG/SMFM guidance and cited studies do not recommend routine clinical use of whole genome sequencing for prenatal diagnosis outside research, and this policy reflects genome sequencing as investigational. The policy also notes that criteria for single-gene prenatal diagnosis were moved to the General policy.

Evidence / Guideline	Key point
ACOG statement (prenatal CMA yield)	CMA identifies clinically significant abnormalities in ~6% of fetuses with ultrasound structural abnormalities and normal karyotype; ~1.7% in fetuses with normal ultrasound and normal karyotype.
Exome sequencing diagnostic yield (NIHF meta-analysis)	Up to 37% of non-immune hydrops fetalis cases have a monogenic disorder detectable by exome sequencing after negative workup.
WGS diagnostic rate (Zhou et al.)	Whole genome sequencing showed a 19.8% diagnostic rate in fetuses with structural anomalies (research context).
Key guideline references	ACMG points to consider (2020), ACOG Practice Bulletins, SMFM committee opinions, and multiple diagnostic utility studies support using CMA as primary test for fetal structural abnormalities and define roles for ES; WGS remains investigational.

Definitions & Thresholds

Major malformations: Structural defects with significant effect on function or appearance; may be lethal or associated with severe/moderate immediate or long-term morbidity (examples by organ system listed in policy, e.g., complex heart malformations, neural tube defects, body wall defects, skeletal disorders, renal agenesis).

Amniocentesis: Procedure in which a sample of amniotic fluid is removed from the uterus for prenatal diagnostic testing.

Chorionic Villus Sampling (CVS): Procedure where a sample of chorionic villi is removed from the placenta for prenatal diagnostic testing.

Percutaneous Umbilical Cord Blood Sampling (PUBS): Procedure where a sample of fetal blood is extracted from the vein in the umbilical cord for prenatal diagnostic testing.

Recurrent pregnancy loss (RPL): Defined as having two or more failed clinical pregnancies, including a current loss if applicable.

Numeric thresholds

Nuchal translucency >=5.0 mmNoonan panel indication

Nuchal translucency >=3.0 mm + additional findingNoonan panel when paired with JLS, hydrops, polyhydramnios, pleural effusion, or cardiac defect

Revision History

11/24revisedLatest

Added PLA code 0496U to CMA prenatal criteria to match policy reference table and added new PLA test to Policy Reference Table.

revised

Updated CMA for pregnancy loss counseling requirements and replaced 'after' with 'at or greater than' regarding gestational age; changed indication wording to include 'history of recurrent pregnancy loss' and 'at or greater than 20 weeks'.

04/24revised

Policy Summary

PayerCentene

PolicyV1.2025 Concert Genetic Testing: Prenatal Diagnosis (via Amniocentesis, CVS, or PUBS) and Pregnancy Loss

Policy CodePolicy N/A

Change TypeRevisions, coding updates, criteria clarifications

Effective DateN/A

Next Review DateN/A

SourceLink

On This Page

Conventional Karyotype Analysis for Prenatal Diagnosis

Conventional karyotype analysis (88235, 88261, 88262, 88263, 88264, 88267, 88269, 88280, 88291) for prenatal diagnosis via amniocentesis, CVS, or PUBS may be considered medically necessary when:

ALL of the following

Member/enrollee has received counseling regarding the benefits and limitations of prenatal screening and diagnostic testing (including karyotyping via amniocentesis, CVS or PUBS) for fetal chromosome abnormalities.

Conventional Karyotype Analysis for Prenatal Diagnosis - Investigational

Investigational when:

ANY of the following

All other indications not meeting the medical necessity criteria above.

CMA for Pregnancy Loss (POC)

Chromosomal microarray analysis (81228, 81229, 81265, 88235) on products of conception (POC) may be considered medically necessary as an alternative to conventional karyotype analysis when:

ALL of the following

ONE of
- Member/enrollee has a history of recurrent pregnancy loss.
- Member/enrollee has a pregnancy loss at or greater than 20 weeks of gestation (i.e., intrauterine fetal demise or stillbirth).>= 20 weeks
Member/enrollee has received counseling regarding the benefits and limitations of chromosome microarray analysis on products of conception.

CMA for Pregnancy Loss - Investigational

Investigational when:

ANY of the following

All other indications not meeting the medical necessity criteria above.

Conventional Karyotype Analysis for Pregnancy Loss (POC)

Conventional karyotype analysis (88235, 88261, 88262, 88263, 88264, 88267, 88269, 88280, 88291) on products of conception (POC) may be considered medically necessary when:

ALL of the following

Member/enrollee has a history of recurrent pregnancy loss.

Conventional Karyotype Analysis for Pregnancy Loss - Investigational

Investigational when:

ANY of the following

All other indications not meeting the medical necessity criteria above.

Prenatal Diagnosis for Noonan Spectrum Disorders/RASopathies

Noonan syndrome panel (81404, 81405, 81406, 81407, 81479, 81442, 81265, 88235) via amniocentesis, CVS, or PUBS may be considered medically necessary when:

ALL of the following

Current pregnancy has had a normal karyotype and/or microarray.
ONE of
- Ultrasound finding of increased nuchal translucency or cystic hygroma of at least 5.0 mm in the first trimester.>= 5.0 mm
- Both of the following
  - An increased nuchal translucency of at least 3.0 mm.>= 3.0 mm
  - AND one of
    Distended jugular lymph sacs (JLS).
    Hydrops fetalis.
    Polyhydramnios.
    Pleural effusion.
    Cardiac defects (e.g., pulmonary valve stenosis, atrioventricular septal defect, coarctation of the aorta, hypertrophic cardiomyopathy, atrial septal defect, etc.).

Prenatal Diagnosis for Noonan Spectrum Disorders/RASopathies - Investigational

Investigational when:

ANY of the following

All other indications not meeting the medical necessity criteria above.

Prenatal Diagnosis for Skeletal Dysplasias

Skeletal dysplasia panel (81404, 81405, 81408, 81479, 81265, 88235) via amniocentesis, CVS, or PUBS may be considered medically necessary when:

ALL of the following

ONE of the following ultrasound findings
- Long bones less than 5th percentile.<= 5th percentile
- Poor mineralization of the calvarium.
- Fractures of long bones (particularly femora).
- Bent/bowed bones.
- Poor mineralization of the vertebrae.
- Absent/hypoplastic scapula.
- Equinovarus.
Panel being ordered includes, at a minimum, the following genes: COL1A1, COL1A2, COL2A1, FGFR3.

Prenatal Diagnosis for Skeletal Dysplasias - Investigational

Investigational when:

ANY of the following

All other indications not meeting the medical necessity criteria above.

Prenatal Diagnosis via Exome Sequencing

Exome sequencing (81415, 81416, 81265, 88235) via amniocentesis, CVS, or PUBS may be considered medically necessary when:

ALL of the following

Current pregnancy has had a karyotype and/or microarray performed and the results were negative/normal.
Alternate etiologies have been considered and ruled out when possible (examples: environmental exposure, injury, infection, maternal condition).
ONE of
- Non-immune hydrops fetalis.
- Two or more major malformations on ultrasound affecting different organ systems.

Prenatal Diagnosis via Exome Sequencing - Investigational

Investigational when:

ANY of the following

All other indications not meeting the medical necessity criteria above.

Prior authorization is likely required by the member's Health Plan. Tests and CPT/PLA codes referenced in this policy are provided for informational purposes and inclusion does not guarantee coverage. Providers should obtain preauthorization per Centene plan procedures and reference the Concert Platform for the current list of registered tests when seeking authorization.

Check Concert Platform for registered tests and up-to-date test listings before submitting a PA request.
Follow Centene plan-specific preauthorization procedures and documentation requirements.

Denial Risk

Investigational indications will be denied

Testing deemed investigational for indications outside the stated medical necessity criteria in this policy will be denied. Coverage is limited to the specific indications listed (e.g., CMA, karyotype, exome sequencing for specified fetal anomalies); all other uses are considered investigational.

Requests for tests for indications not meeting the policy criteria may be denied as investigational.
Genome sequencing for prenatal diagnosis is listed as investigational in the policy.

Documentation Required

Reference and coding updates must be applied

Providers and billing staff must apply the updated coding when submitting claims and documenting medical necessity. The policy reference table and criteria set were updated to include PLA code 0496U for Chromosomal Microarray Analysis (CMA); ensure this PLA code and any other revised codes are used where appropriate on claims and authorization requests.

Apply PLA code 0496U (added to the CMA criteria set) on relevant CMA test claims and documentation.
Verify CPT/PLA codes in the Concert Platform and the policy reference table prior to billing.

Prior Authorization

Policy subject to Health Plan-level determination and medical necessity

Coverage decisions require application of the clinical policy medical necessity criteria and are subject to Health Plan terms, conditions, exclusions, and applicable state/federal requirements. Providers should obtain prior authorization where required by the Health Plan and confirm benefits prior to performing testing.

Obtain prior authorization from the member's Health Plan when required.
Confirm that the requested test and indication meet the plan's medical necessity criteria and benefit terms.

Pregnancy loss gestational age threshold>= 20 weeks for CMA on POC

Recurrent pregnancy loss definition2 or more failed clinical pregnancies (RPL)

Expanded and clarified criteria for Noonan spectrum disorders: lowered nuchal translucency threshold to 3.0 mm when additional findings are present, removed minimum gene list for RASopathies, and included panels/codes.

revised

Moved prenatal diagnosis for single-gene disorders criteria to General policy and added multiple single-gene and panel CPT codes to the policy reference table (coding additions/removals).

removed

Removed one criterion regarding exome or genome sequencing for pregnancy loss on products of conception due to lack of volume in claims.

revised

Background and Rationale reformatted; references updated and minor rewording for clarity throughout the policy.

added

Added PLA code 0496U to the Chromosomal Microarray Analysis (CMA) criteria set (coding update to match Policy Reference Table).

moved

Prenatal Diagnosis for Single Gene Disorders criteria relocated to the General policy (no change to clinical criteria content).

removed

Reference update in Background and Rationale and References sections (removed out-of-date reference and added new reference in Prenatal Diagnosis via Exome Sequencing).