MA Reproductive Testing: Prenatal Diagnosis (Preauthorization Required)
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Defines medical necessity, preauthorization expectations, and coverage criteria for prenatal diagnostic genetic tests (CMA, exome, genome, targeted panels) via invasive sampling and for chromosomal microarray on products of conception; applies to Blue Cross Blue Shield - Nebraska members.
No material clinical or coverage changes in this revision.
Coverage Criteria for Prenatal and Pregnancy-loss Genetic Testing
inv-01: Prenatal CMA — Covered when ALL of the following are met
Covered when ALL of the following are met
Chromosomal microarray analysis for prenatal diagnosis is considered not reasonable and necessary for all other indications.
inv-02: Prenatal Exome Sequencing — Covered when ALL of the following are met
Covered when ALL of the following are met
Prenatal exome sequencing is considered not reasonable and necessary for all other conditions; pretest counseling by a genetics professional and rapid laboratory turnaround time are recommended.
inv-03: Prenatal Genome Sequencing — 1 top-level node
No indications covered.
inv-04: Pregnancy Loss (POC) CMA — Covered when ONE of the following are met AND counseling provided
Covered when ONE of the following is met AND counseling provided
Chromosomal microarray analysis on POC is considered not reasonable and necessary for all other indications.
inv-05: Noonan Spectrum Disorders / RASopathies — Covered when ALL of the following are met
Covered when ALL of the following are met
Prenatal testing for Noonan spectrum disorders is considered not reasonable and necessary for all other indications.
inv-06: Skeletal Dysplasias — Covered when ALL of the following are met
Covered when ALL of the following are met
Prenatal skeletal dysplasia panels are considered not reasonable and necessary for all other indications.
inv-07: Medically Necessary Indications (society-aligned) — Covered when aligned with professional society recommendations and clinical indications:
Covered when aligned with professional society recommendations and clinical indications:
ACOG and ACOG-SMFM guidance support CMA replacing karyotype for structural anomalies.
ACOG practice bulletin notes this exception.
ACMG points to consider and society statements referenced.
ISPD and ACOG/SMFM statements indicate limited routine use.
ACOG/SMFM committee opinion and ASRM literature support CMA for products of conception.
Prenatal genome sequencing (whole-genome sequencing performed on fetal samples obtained via amniocentesis, CVS, or PUBS) is excluded for all indications under this policy and is considered not reasonable and necessary (no clinical circumstances are listed where prenatal genome sequencing is covered).
This exclusion aligns with the policy text which explicitly states that prenatal genome sequencing is considered not reasonable and necessary for all indications.
Routine use of whole-genome sequencing (WGS) or whole-exome sequencing (WES) for prenatal diagnosis is not recommended outside the context of clinical trials until sufficient peer‑reviewed data and validation studies are published. Professional society guidance cited by the policy (ACOG/SMFM and ISPD) supports limiting routine prenatal WES/WGS to research or select validated clinical contexts.
Providers should therefore consider WGS/WES prenatally only within research protocols or when supported by specific, validated clinical indications described elsewhere in this policy.
There are no additional exclusions or exception statements listed in this section beyond those explicitly described for prenatal genome sequencing and routine prenatal WES/WGS use.
Each coverage section in this policy defines specific clinical indications that meet medical necessity and expressly indicates that testing is not reasonable and necessary for other indications outside those listed. Examples include prenatal CMA, prenatal exome sequencing, prenatal genome sequencing, CMA on products of conception (POC), Noonan/RASopathy panels, and skeletal dysplasia panels.
Prior authorization and the specific clinical criteria must be met for coverage; tests performed for indications not enumerated in the applicable section are subject to denial as not reasonable and necessary.
The policy references ACOG/SMFM and ISPD guidance which advise against routine clinical use of WGS/WES for prenatal diagnosis outside of research or carefully validated settings. Consequently, routine deployment of WGS/WES in prenatal care without a research context or validated indication is considered inappropriate per those society statements.
In the portions of the source cited for coding and general statements, there are no additional explicit sections labeled ‘not medically necessary’ beyond the policy’s per-section statements that tests are not reasonable and necessary for indications outside the listed criteria.
Procedure and Billing Codes
| 81228 | Listed in CMA and pregnancy loss CMA reference table |
| 81229 | Listed in CMA and pregnancy loss CMA reference table |
| 81265 | Listed in multiple sequencing and panels reference table |
| 81349 | Listed in CMA reference table |
| 81479 | Unlisted molecular pathology code referenced in tables |
| 0469U | IriSight CNV Analysis - Prenatal (Variantyx) referenced |
| 81415 | Exome sequencing code referenced for prenatal exome |
| 81416 | Exome sequencing code referenced for prenatal exome |
| 81425 | Whole genome sequencing code referenced |
| 81426 | Whole genome sequencing code referenced |
| No codes listed |
| 0582U | RARE DS RPD WHL GEN DNA SEQ SNVS INDELS VARIANTS |
| 0583U | RARE DS RPD WHL GEN CMPTR DNA SEQ VRNTS PROBAND |
| 81210 | BRAF GENE ANALYSIS V600E VARIANT |
| 81228 | CYTOGENOM CONST MICROARRAY COPY NUMBER VARIANTS |
| 81229 | CYTOGENOM CONST MICROARRAY COPY NUMBER&SNP VAR |
| 81265 | COMPARATIVE ANAL STR MARKERS PATIENT&COMP SPEC |
| 81266 | COMPARATIVE ANAL STR MARKERS EA ADDL SPECIMEN |
| 81349 | CYTOG ALYS CHRMOML ABNOR LOW-PASS SEQ ALYS |
| 81404 | MOLECULAR PATHOLOGY PROCEDURE LEVEL 5 |
| 0582U | RARE DS RPD WHL GEN DNA SEQ SNVS INDELS VARIANTS |
| 0583U | RARE DS RPD WHL GEN CMPTR DNA SEQ VRNTS PROBAND |
| 81404 | MOLECULAR PATHOLOGY PROCEDURE LEVEL 5 |
| 81405 | MOLECULAR PATHOLOGY PROCEDURE LEVEL 6 |
| 81406 | MOLECULAR PATHOLOGY PROCEDURE LEVEL 7 |
| 81407 | MOLECULAR PATHOLOGY PROCEDURE LEVEL 8 |
| 81408 | MOLECULAR PATHOLOGY PROCEDURE LEVEL 9 |
| 81415 | EXOME SEQUENCE ANALYSIS |
| 81416 | EXOME SEQUENCE ANALYSIS EACH COMPARATOR EXOME |
| 81425 | GENOME SEQUENCE ANALYSIS |
| 81426 | GENOME SEQUENCE ANALYSIS EACH COMPARATOR GENOME |
| 81442 | NOONAN SPECTRUM DISORDERS GEN SEQ ANALYS 12 GEN |
Provider Requirements, Preauthorization, and Documentation
Preauthorization required for prenatal diagnostic genetic tests
Submit preauthorization for any prenatal diagnostic genetic test listed in this policy; include the procedure code and corresponding diagnosis code pair when requesting review. The policy title and header designate these tests as "Preauthorization Required."
- Quick Code Search requires entering a procedure code then a diagnosis code and clicking "Add Code Pair."
- If the codes are listed in this policy the Quick Code Search will display a dropdown to assist.
Preauthorization required for listed genetic testing codes
Preauthorization is required for sequencing, microarray, and selected molecular procedure codes when used for prenatal diagnosis or pregnancy loss evaluation; include the specific CPT/PLA/HCPCS code(s) on the authorization request.
Preauthorization required for listed prenatal diagnostic codes
Preauthorization must be obtained for the prenatal diagnostic and molecular pathology tests and billing codes enumerated in the policy's code tables before testing is performed.
Required prior testing steps before approval
Follow the policy's required sequencing of testing: exome sequencing requests must document prior negative/normal karyotype and/or microarray results; authorization is contingent on those prior tests having been performed and reviewed.
- Prenatal exome: member's current pregnancy must have had karyotype and/or microarray performed with negative/normal results before exome is considered.
- Policy language indicates CMA is primary for structural anomalies and exome is considered when CMA/karyotype are non-diagnostic.
Preferred testing sequence for fetal structural anomalies
When fetal structural anomalies are detected, submit CMA as the primary diagnostic test (it can replace conventional karyotype); if a specific aneuploidy is suspected document why karyotype (with or without FISH) is being performed first.
- ACOG recommends offering CMA to any patient undergoing invasive diagnostic testing and as the primary test when fetal structural abnormalities are detected.
- The policy allows karyotype first if features suggest a specific aneuploidy.
Document counseling about benefits and limitations
Document that the member received counseling about the benefits and limitations of prenatal screening and diagnostic testing (including CMA) when counseling is specified; include counseling notes with the preauthorization submission where applicable.
- Policy criteria require that the member has received counseling regarding benefits and limitations for prenatal CMA and for CMA on products of conception.
- Counseling is a stated coverage criterion and is required for consideration of CMA in prenatal and POC settings.
Genetics counseling and laboratory turnaround documentation
For fetal exome sequencing, include documentation of pretest counseling by a genetics professional and note laboratory turnaround-time expectations; post-test counseling should be arranged and documented regardless of result.
- ACMG guidance recommends pretest counseling by a genetics professional and that laboratories offering prenatal ES have clearly defined rapid turnaround times.
- Post-test counseling by individuals with relevant expertise is recommended regardless of test result.
Include guideline references with prior authorization
Submit preauthorization requests with clinical documentation referencing guideline support where relevant (e.g., ACOG practice bulletins and ACOG–SMFM committee opinions cited in the policy) to support medical necessity determinations.
- Policy references ACOG Practice Bulletin No.162 and ACOG–SMFM Committee Opinion No.682 among literature cited in the References section.
Denial risk: prenatal CMA outside criteria
CMA for prenatal diagnosis is considered not reasonable and necessary for indications that do not meet the policy criteria (member must have counseling and must not be simultaneously undergoing karyotype analysis).
- Policy states CMA is considered reasonable and necessary only when counseling is provided and the member is not simultaneously undergoing karyotype; all other indications are not reasonable and necessary.
Denial risk: prenatal exome outside specified indications
Prenatal exome sequencing will be denied if requested for conditions outside the specified criteria; authorization requires documentation of prior negative/normal karyotype and/or microarray, consideration of alternate etiologies, and qualifying fetal findings.
- Covered indications require prior negative/normal karyotype/microarray and either non-immune hydrops fetalis or two or more major malformations on ultrasound affecting different organ systems.
- Exome sequencing is not reasonable and necessary for all other conditions.
Denial risk: prenatal genome sequencing (all indications)
Prenatal genome sequencing is considered not reasonable and necessary for all indications and authorization requests for prenatal genome sequencing will be denied.
- Policy explicitly states prenatal genome sequencing is not reasonable and necessary for any indication.
Denial risk: POC CMA outside criteria
Chromosomal microarray analysis on products of conception (POC) will be denied if the request does not meet policy criteria; covered POC CMA requires a history of recurrent pregnancy loss or a loss at ≥20 weeks and documentation that counseling was provided.
- Policy requires either recurrent pregnancy loss or pregnancy loss at or ≥20 weeks gestation plus counseling regarding benefits and limitations of CMA on POC.
- POC CMA is not reasonable and necessary for all other indications.
Include procedure + diagnosis code pair on authorization
Ensure the preauthorization request includes both the specific procedure code and the diagnosis code pair; failure to submit both may prevent the Quick Code Search from assisting and could delay review or lead to hold/denial.
- Quick Code Search workflow: enter procedure code, then diagnosis code, then click "Add Code Pair."
- The policy warns that omission of the diagnosis/procedure pair can impede automated assistance.
Preauthorization requirement (policy header)
Tests listed in the policy header require preauthorization prior to performance; do not proceed with testing without an approved authorization.
- Policy title includes the phrase "Preauthorization Required," establishing the preauthorization expectation for the listed tests.
Background: counseling and test purpose
Background: prenatal diagnostic genetic tests (CMA, exome, genome, targeted panels) are used to identify fetal genetic conditions in pregnancies at increased risk; genetic counseling is strongly recommended prior to testing.
- Policy description emphasizes joint decision-making between patient and clinician and strongly recommends genetic counseling.
Background and Rationale
Prenatal diagnostic genetic testing (including chromosomal microarray analysis, exome sequencing, genome sequencing, and targeted panels) is used to identify fetal genetic conditions in pregnancies at increased risk and to evaluate causes of pregnancy loss. The policy requires counseling where specified and recommends CMA as the primary test when structural fetal anomalies are present; exome sequencing may be considered when CMA/karyotype are non-diagnostic and specific criteria (such as non-immune hydrops fetalis or multiple major malformations) are met.
Genetic counseling is emphasized prior to testing, and preauthorization is required for listed tests and associated CPT/HCPCS codes.
Definitions and Test Descriptions
Policy Revision History
Policy M.69 original effective date established.
Policy underwent last review on 2026-01-28 prior to effective date.
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