Aetna CGH Coverage Policy Update

Prenatal and fetal indications

Covered when ANY of the following are met for prenatal and certain dermatologic indications:

Prenatal/fetal: Evaluating fetuses with structural abnormalities detected on fetal ultrasound or fetal MRI; OR for pregnant women undergoing invasive prenatal diagnostic testing (amniocentesis or chorionic villus sampling) for any indication; OR analyses of fetal tissue (amniotic fluid, placenta, or products of conception) in the evaluation of intrauterine fetal death or stillbirth (>=20 weeks gestation).

Dermatologic (Spitzoid) indication

Covered when ANY of the following are met:

Spitzoid neoplasms: Evaluation of histologically equivocal spitzoid melanocytic neoplasms (Spitz nevus and atypical Spitz tumors) to assist distinction between benign Spitz lesions and spitzoid melanoma when histopathology and immunohistochemistry are inconclusive.

Molecular analysis (CGH or aCGH) is adjunctive to histopathologic assessment and immunostaining.

Children with congenital anomalies

Covered for diagnosing genetic abnormalities in children when ALL of the following are met:

Pediatric congenital anomalies: 1) The member's clinical presentation is not specific to a well-delineated genetic syndrome; AND 2) The child has one or more of: two or more major malformations; OR a single major malformation or multiple minor malformations in an infant/child born with intrauterine growth restriction (IUGR) or small for gestational age; OR a single major malformation and multiple minor malformations; AND 3) Evaluated by a Board-Certified or Board-Eligible Medical Geneticist, Developmental/Behavioral Pediatrician, or Pediatric/Adult Neurologist to determine if CGH is warranted; AND 4) Results have the potential to impact management.

See Appendix for specifics of major/minor malformations.

Developmental delay/intellectual disability or autism spectrum disorder

Covered for children with DD/ID or ASD when ALL of the following are met:

DD/ID or ASD: 1) Targeted genetic testing (e.g., FMR1 for Fragile X), if indicated by clinical or family history, is negative; AND 2) The member's clinical presentation is not specific to a well-delineated genetic syndrome; AND 3) Evaluated by a Board-Certified or Board-Eligible Medical Geneticist, Developmental/Behavioral Pediatrician, or Pediatric/Adult Neurologist to evaluate if CGH is warranted; AND 4) Results have the potential to impact clinical management.

DSM-5 criteria referenced for DD/ID or ASD.

Supported clinical contexts

Contexts in which CMA/CGH is supported or specifically recommended by cited guidelines and studies

Prenatal with fetal structural anomalies: Microarray analysis identifies additional clinically significant cytogenetic information compared with karyotype and may be used instead of karyotype when fetal structural anomalies are present and rapid aneuploidy screening is negative and appropriate turnaround time is assured (Wapner 2012).

Does not detect balanced translocations or triploidy; counseling regarding variants of uncertain significance recommended.

Postnatal evaluation of intellectual disability, autism, multiple congenital anomalies: ACMG standards recommend genomic microarrays as first-tier postnatal tests for individuals with intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies (ACMG guidance).

Higher diagnostic yield than karyotype; requires genetics expertise for interpretation.

Products of conception / stillbirth evaluation: Chromosomal microarray analysis is recommended for evaluation of fetal tissue (eg, amniotic fluid, placenta, products of conception) because it yields a higher rate of results than karyotyping and can identify maternal cell contamination (ACOG Committee Opinion).

Spitzoid melanocytic neoplasms

Use of CGH for spitzoid melanocytic lesions:

Spitzoid lesion CGH use: CGH or array-CGH may be used when histopathologic and immunohistochemical evaluation of a spitzoid melanocytic lesion remains equivocal for benign versus malignant behavior; absence of aberrations or isolated 11p gain favors benign Spitz lesion, whereas multiple aberrations characteristic of conventional melanoma suggest malignancy.

Supported by multiple studies and UpToDate/NCCN guidance; Ki‑67 >30% favors melanoma but overlap exists.

Primary ovarian insufficiency (POI)

Use of array-CGH in primary ovarian insufficiency:

POI genetic evaluation: High-resolution array-CGH may identify ovary-related copy-number variants in patients with early-onset primary ovarian insufficiency and can complement next-generation sequencing as part of comprehensive genetic evaluation.

Study identified ovary-related CNVs in 32 of 67 patients; array‑CGH plus NGS may increase diagnostic yield.

Neurodevelopmental disorders / developmental delay

Chromosomal microarray testing for neurodevelopmental disorders:

Neurodevelopmental evaluation: Chromosomal microarray (eg, FirstStepDX Plus) is used to identify copy-number variants in patients with autism spectrum disorder, developmental delay, or intellectual disability; buccal swab collection is validated versus blood and reported diagnostic yields include ~9.5% pathogenic findings, 20.2% VOUS, and ~29.7% overall CNV yield in the FSDX cohort.

Testing should follow validated laboratory standards; results require genetics expertise for interpretation.

Aetna considers comparative genomic hybridization (CGH) not medically necessary when a diagnosis of a disorder or syndrome is readily apparent from clinical evaluation alone. This policy also limits medically necessary CGH testing in the pediatric congenital anomaly and neurodevelopmental indications to cases that meet the specific criteria (e.g., non‑specific presentation, specialist evaluation, and potential for test results to impact management); evaluations that do not meet those criteria are considered not medically necessary. Only one CGH is considered medically necessary per lifetime when criteria are met.

Array genomic hybridization is not recommended for routine prenatal diagnosis in pregnancies at low risk for structural chromosomal abnormalities (for example: advanced maternal age alone, positive maternal serum screen, previous trisomy, or isolated soft ultrasound markers). When fetal structural anomalies are present, microarray may be appropriate and can be performed in lieu of karyotype if rapid aneuploidy screening is negative and an acceptable turnaround time for results is assured.

Several UpToDate topic reviews referenced in the policy do not list CGH as a management option for certain conditions. Specifically, UpToDate summaries for spontaneous primary ovarian insufficiency, short stature, and craniosynostosis do not mention comparative genomic hybridization as part of routine management, indicating limited support for CGH in these contexts.

Testing of products of conception for pregnancy losses is guided by gestational age and clinical context. Aetna considers chromosomal microarray analysis appropriate for evaluation of fetal tissue in intrauterine fetal death or stillbirth at ≥20 weeks gestation; however, testing products of conception in pregnancy losses at <20 weeks in structurally normal embryos/fetuses (including first‑trimester and recurrent losses) is considered experimental and investigational and therefore not covered.

Array genomic hybridization is not recommended for routine use in pregnancies at low risk for structural chromosomal abnormalities (eg, advanced maternal age alone, positive maternal serum screen, previous trisomy, or isolated soft ultrasound markers). Professional guidance recommends pre‑test consultation with a medical geneticist for pregnant women who qualify for microarray testing to discuss benefits, limitations, and possible outcomes.

UpToDate reviews for several topics (including atypical/dysplastic nevi in the context of melanoma history, primary ovarian insufficiency, short stature, and craniosynostosis) do not include comparative genomic hybridization as a management option, reinforcing that CGH is not routinely recommended for these indications in current clinical summaries.

Specified Covered Indications

Summary of covered indications

Summary of covered indications: Prenatal diagnosis for fetuses with structural abnormalities; invasive prenatal diagnostic testing for any indication; stillbirth/products of conception analyses >=20 weeks; postnatal diagnosis in children with congenital anomalies meeting listed malformation criteria; adjunct testing for histologically equivocal spitzoid melanocytic neoplasms; children with DD/ID or ASD when targeted testing is negative and specialist evaluation documented.

Only one CGH is considered medically necessary per lifetime; specialist evaluation and, in prenatal cases, genetic consultation are recommended as noted in policy.

Evaluation of fetuses with structural anomalies

Fetal structural anomalies evaluation: Microarray analysis may be performed to evaluate fetuses with structural anomalies detected on ultrasound or fetal MRI and can be used in lieu of karyotype when rapid aneuploidy screening is negative and turnaround time is acceptable; microarray identifies additional clinically significant findings compared with karyotype (Wapner 2012).

Does not detect balanced translocations or triploidy; counseling about VOUS recommended.

Postnatal first-tier testing for intellectual disability/ASD/multiple congenital anomalies

Postnatal first-tier testing: Chromosomal microarray is recommended as a first‑tier postnatal test for individuals with intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies per ACMG standards and guideline updates.

Higher diagnostic yield than karyotype; interpretation requires genetics expertise.

Evaluation of intrauterine fetal death or stillbirth

Stillbirth / intrauterine fetal death evaluation: Chromosomal microarray analysis is recommended for evaluation of intrauterine fetal death or stillbirth and products of conception when further cytogenetic analysis is desired because it increases the likelihood of obtaining results and can identify maternal cell contamination.>=20 weeks

ACOG Committee Opinion and NICHD stillbirth research support CMA utility in stillbirth evaluation.

Adjunct diagnostic aid for histologically equivocal spitzoid melanocytic neoplasms

Adjunct diagnostic aid for spitzoid lesions: Use of CGH as an adjunct diagnostic tool is supported for histologically equivocal spitzoid melanocytic neoplasms to help distinguish benign Spitz lesions from spitzoid melanoma when morphology and immunohistochemistry are inconclusive.

Absence of chromosomal aberrations or isolated 11p amplification favors benign lesion; multiple melanoma‑typical alterations (eg, deletions in 9p, 10q; gains in Chr7) suggest malignancy.

Histologically equivocal spitzoid melanocytic neoplasms

Histologically equivocal spitzoid lesions: CGH may be used for histologically equivocal spitzoid melanocytic neoplasms to aid distinction between Spitz nevus/atypical Spitz tumor and spitzoid melanoma, per UpToDate and NCCN guidance.

Ki‑67 labeling index >30% favors melanoma but overlap exists; molecular testing is adjunctive.

Genetic evaluation of autism spectrum disorder, developmental delay, and intellectual disability

Genetic evaluation for ASD/DD/ID: Chromosomal microarray testing (including platforms such as FirstStepDX Plus) is appropriate for genetic evaluation of autism spectrum disorder, developmental delay, and intellectual disability; buccal swab collection is validated and reported diagnostic yields provided in validation studies.

Reported FSDX yields: pathogenic 9.5%, VOUS 20.2%, overall 29.7%.

Evaluation of primary ovarian insufficiency to identify ovary-related CNVs

POI evaluation by array-CGH: High‑resolution array‑CGH may be used in the evaluation of primary ovarian insufficiency to identify ovary‑related CNVs that could contribute to early‑onset POI and can complement NGS in comprehensive assessment.

Study identified 32 patients with ovary‑related CNVs among 67 cases; combined approaches recommended.

Genetic evaluation in specified clinical contexts

Genetic evaluation contexts: Chromosomal microarray is supported for genetic evaluation in cases of developmental delay/intellectual disability, autism spectrum disorder, multiple congenital anomalies, prenatal diagnosis (including stillbirth), and neonates with birth defects where further cytogenetic analysis is desired.

Testing and interpretation should follow established laboratory standards and clinical genetics evaluation.

Coding and Billing

Covered CPT CodesCPTCovered

81228	Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number variants (eg, bacterial artificial chromosome [BAC] or oligo-based comparative genomic hybridization [CGH] microarray analysis).
81229	Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number and single nucleotide polymorphism (SNP) variants for chromosomal abnormalities.
81277	Cytogenomic neoplasia (genome-wide) microarray analysis, interrogation of genomic regions for copy number and loss-of-heterozygosity variants for chromosomal abnormalities.
81349	Cytogenomic (genome-wide) analysis for constitutional chromosomal abnormalities; interrogation of genomic regions for copy number and loss-of-heterozygosity variants, low-pass sequencing analysis.
0156U	Copy number (eg, intellectual disability, dysmorphology), sequence analysis.

Covered HCPCS CodesHCPCSCovered

S3870

Comparative genomic hybridization (CGD) microarray testing for developmental delay, autism spectrum disorder and/or intellectual disability.

Relevant ICD-10 Codes (covered/used for selection)ICD-10

D22.0 - D22.9	Melanocytic nevi [Spitzoid melanocytic neoplasms].
F01 - F99	Mental, behavioral and neurodevelopmental disorders.
O35.0xx0	Maternal care for (suspected) central nervous system malformation in fetus.
P95	Stillbirth.
Q00.0 - Q99.9	Congenital malformations, deformations and chromosomal abnormalities.
Z36.0 - Z36.9	Encounter for antenatal screening of mother.
Z37.1	Single stillbirth.

ICD-10 Codes Listed as Experimental/Not CoveredICD-10Not Covered

C43.0 - C43.9	Malignant melanoma of skin (listed as not covered indication).
D89.82	Autoimmune lymphoproliferative syndrome [ALPS] (listed as not covered indication).
E28.310 - E28.39	Primary ovarian failure [evaluation of primary ovarian insufficiency] (listed as not covered indication).
G40.001 - G40.919	Epilepsy and recurrent seizures (listed as not covered indication).
N96	Recurrent pregnancy loss (listed as not covered indication).
Q75.0	Craniosynostosis (listed as not covered indication).

Covered/Referenced Codesmixed

not specified

No specific CPT/HCPCS/ICD codes are provided in this segment of the document.

Age for certain pediatric indications

Policy populationApplies to pediatric patients for congenital anomalies, DD/ID, and ASD; evaluation of individuals older than 18 years for congenital anomalies/ASD/DD/ID is considered experimental and investigational (not covered)

Specialist evaluation requiredTesting for pediatric congenital anomalies and for DD/ID or ASD requires evaluation by a Board‑Certified or Board‑Eligible Medical Geneticist, Developmental/Behavioral Pediatrician, or Pediatric/Adult Neurologist

Lifetime frequencyOnly one CGH is considered medically necessary per lifetime

Targeted testing prerequisiteTargeted genetic testing (e.g., FMR1 for Fragile X) should be performed and be negative when indicated prior to CGH for DD/ID or ASD

Ki-67 labeling index

Ki‑67 threshold> 30% Ki‑67 labeling index (in deepest part of lesion) favours melanoma over Spitz lesion, though overlap exists

Role in evaluationKi‑67 labeling index is used alongside histopathology and immunohistochemistry to help distinguish atypical Spitz tumors from melanoma

Interpretation caveatConsiderable overlap exists between atypical Spitz tumors and melanoma; molecular testing may be needed if diagnosis remains uncertain

Provider Actions and Administrative Guidance

Prior Authorization

Code coverage contingent on criteria

CPT/HCPCS codes for CGH are covered only when the clinical selection criteria in this policy are met; prior authorization may be required per payer processes. Documentation should show how the clinical indications meet policy criteria (e.g., prenatal structural abnormalities, DD/ID/ASD criteria, histologically equivocal spitzoid lesions).

Codes (e.g., CPT 81228, 81229, 81277, 81349; HCPCS S3870; CPT 0156U) are covered only if selection criteria in this policy are satisfied.
Ordering clinicians should include clinical documentation that supports the indication and specialist evaluation when applicable.

Documentation Required

Prenatal testing: use with structural anomalies

In prenatal cases with fetal structural abnormalities detected on ultrasound or fetal MRI, chromosomal microarray (array CGH) may be used in lieu of karyotype if rapid aneuploidy screening is negative and an appropriate turnaround time is assured. This use should be accompanied by specialist consultation and informed discussion of benefits and limitations.

Array CGH is not recommended in pregnancies at low risk for structural chromosomal abnormality.
Pre-test genetic consultation by a medical geneticist is recommended for pregnant women who qualify for microarray testing.

Prior Authorization

Prior authorization guidance

Prior authorization guidance is not explicitly listed in the excerpt for specific CPT/HCPCS codes; however, prior authorization may be required per payer processes and is recommended when clinical documentation or histopathology is equivocal (for example, spitzoid lesions) or when policy-specified indications are used.

If your plan requires prior authorization, submit clinical notes, specialist evaluation, and evidence that policy criteria are met.
When histopathology is equivocal for spitzoid lesions, include dermatopathology reports and documentation of multi-disciplinary review.

Note

Prior authorization not specified in excerpt

The document excerpt does not state specific prior authorization requirements for CGH in this section; check payer-specific procedures and prior authorization tools for any required submission steps before testing.

Absence of explicit PA language in the excerpt does not preclude payer-level PA requirements.
Contact the payer or use the payer portal to confirm prior authorization rules and required documentation.

Denial Risk

Experimental / Investigational exclusions

Aetna considers CGH experimental and investigational (and therefore not covered) for certain indications due to insufficient evidence (e.g., detection of balanced rearrangements, diagnosis of melanoma, evaluation of primary ovarian insufficiency, testing products of conception in structurally normal embryos/fetuses <20 weeks, and other listed indications).

Do not submit claims for CGH for indications listed as experimental/investigational; include alternative diagnostic rationale if disputing coverage.
Refer to the policy's Experimental and Investigational section for the not-covered list before ordering.

Documentation Required

Use of array genomic hybridization is not recommended in low-risk pregnancies

Array genomic hybridization is not recommended in pregnancies at low risk for structural chromosomal abnormality and is intended primarily for cases with structural anomalies or other policy-specified indications.

Low-risk indications (advanced maternal age alone, positive serum screen, soft markers) do not by themselves justify array CGH per guidance.
Ensure the indication aligns with policy criteria to avoid denials.

Note

Policy bulletins are intended to assist administration of plan benefits

Clinical Policy Bulletins are intended to assist in administering plan benefits and provide only a partial description of plan or program benefits. They do not guarantee coverage and do not substitute for plan benefit documents or medical advice.

Plan benefit terms and member-specific coverage determinations prevail over the bulletin.
Providers remain responsible for medical advice and should confirm coverage with the payer.

Documentation Required

Pre-test genetic consultation recommended

Pregnant women who qualify for microarray genomic hybridization testing should have pre-test consultation with a medical geneticist so that benefits, limitations, and interpretation challenges (including variants of uncertain significance) are discussed to support informed decision-making.

Document that pre-test counseling occurred and that the patient was informed of possible outcomes and limitations.
Include the consulting geneticist's evaluation in the authorization/claims submission when required.

Documentation Required

Products of conception evaluation

For evaluation of fetal tissue (products of conception, placenta, or other fetal tissue) in intrauterine fetal death or stillbirth (≥ 20 weeks gestation), chromosomal microarray analysis is recommended because it increases the likelihood of obtaining informative results compared with conventional cytogenetics.

Testing of products of conception in pregnancy losses < 20 weeks in structurally normal embryos/fetuses is listed as experimental/investigational and not covered.
When ordering for ≥ 20 weeks stillbirth or intrauterine fetal death, include gestational age and clinical context in documentation.

Documentation Required

Specialist evaluation and documentation required

Ordering of CGH should be informed by evaluation from an appropriate specialist (Board‑Certified or Board‑Eligible Medical Geneticist, Developmental/Behavioral Pediatrician, Pediatric or Adult Neurologist, or other relevant specialist) when required by the policy, and documentation of that evaluation should be included with any authorization request.

Specialist evaluation is required for pediatric congenital anomalies and for DD/ID or ASD indications per the policy criteria.
The excerpt does not explicitly restrict ordering to specialty providers only, but specialist documentation is an explicit policy requirement.

Eligibility Requirements

Eligibility for CGH testing depends on meeting the policy's covered‑indication criteria. The policy provides top‑level guidance on medically necessary indications (prenatal structural anomalies, invasive prenatal diagnostic testing, stillbirth ≥20 weeks, histologically equivocal spitzoid lesions, and certain pediatric congenital anomalies and neurodevelopmental disorders) and on investigational/not covered uses; details and specific documentation requirements are described in the coverage criteria and related sections.

The policy excerpt does not specify detailed family history thresholds. It emphasizes that interpretation of CGH results requires genetics expertise and recommends pre‑test consultation or counseling by a medical geneticist in prenatal cases. Clinical and family history should guide any indicated targeted testing (for example, FMR1) prior to array testing when appropriate.

No additional top‑level eligibility nodes are specified in the provided excerpt beyond the medical necessity criteria already outlined; eligibility decisions should follow the policy criteria and supporting documentation requirements.

No additional top‑level eligibility nodes are specified in the provided excerpt beyond the medical necessity criteria already outlined; see coverage criteria for specific clinical scenarios and documentation requirements.

In prenatal settings, chromosomal microarray may be performed instead of karyotype when fetal structural anomalies are identified and rapid aneuploidy screening is negative, provided that an appropriate turnaround time for results is assured. The policy and cited guidance note that not all prenatal cases require microarray and that counseling about possible variants of uncertain significance is important prior to testing.

Background and Definitions

Background: Comparative genomic hybridization (CGH), also referenced as chromosomal microarray analysis (CMA or aCGH), is a genome‑wide method to detect copy number variants (microdeletions and microduplications) across the genome with greater resolution than conventional karyotype. CGH is used in prenatal and postnatal settings to increase detection of clinically significant chromosomal imbalances, though it does not reliably detect balanced rearrangements and may identify variants of uncertain clinical significance that require genetics expertise for interpretation.

Comparative genomic hybridization (CGH)/chromosomal microarray analysis (CMA)

DefinitionComparative genomic hybridization (CGH) is a genome‑wide method to identify copy‑number variants (microdeletions and microduplications) with greater resolution than karyotype, used to detect genomic imbalances and mosaic abnormalities

SynonymsAlso referred to as chromosomal microarray analysis (CMA) and array CGH (aCGH)

Clinical scopeInvestigated and used for evaluation of congenital anomalies, developmental delay/intellectual disability, autism spectrum disorder, and prenatal testing when structural anomalies are present

Chromosomal microarray analysis (CMA) / array comparative genomic hybridization (aCGH)

DefinitionChromosomal microarray analysis (CMA) / array comparative genomic hybridization (aCGH) is a genome‑wide assay that assesses DNA copy‑number changes (deletions/duplications) with higher resolution than karyotype, including BAC, oligonucleotide, and SNP‑based platforms

Clinical recommendationACMG recommends genomic microarrays as first‑tier postnatal test for individuals with intellectual disability, autism spectrum disorders, or multiple congenital anomalies

LimitationsDoes not reliably detect balanced translocations or polyploidy and may yield variants of uncertain significance requiring genetics expertise

Spitzoid melanocytic neoplasms

DefinitionSpitzoid melanocytic neoplasms are a spectrum that includes Spitz nevus, atypical Spitz tumor, and spitzoid melanoma characterized by spindle and epithelioid melanocytes and sometimes challenging histopathology

Diagnostic challengeHistopathologic and immunohistochemical features can be ambiguous; molecular testing (CGH/FISH) may be performed for ambiguous lesions

Molecular patternsSpitz tumors may show isolated gains (eg, 11p amplification) while melanomas typically have multiple chromosomal copy‑number aberrations

Primary ovarian insufficiency (POI)

DefinitionPrimary ovarian insufficiency (POI) is cessation of ovarian function before age 40; genetic causes are heterogeneous

Role of array‑CGHHigh‑resolution array‑CGH can identify ovary‑related copy‑number variants (CNVs) and may complement next‑generation sequencing in comprehensive evaluation

Study findingIn a cohort of early‑onset POI patients, array‑CGH identified ovary‑related CNVs in 32 of 67 patients

Array comparative genomic hybridization (aCGH)

DefinitionArray comparative genomic hybridization (aCGH) is a genomic copy‑number microarray analysis technique for detecting chromosomal imbalances and copy‑number variants across the genome

Platform typesIncludes targeted aCGH and whole‑genome higher‑density oligonucleotide arrays, which increase sensitivity but may complicate interpretation

Clinical useUsed for prenatal and postnatal detection of copy‑number variants and chromosomal imbalances as an alternative or adjunct to karyotype in specific indications

Constitutional cytogenomic microarray

DefinitionConstitutional cytogenomic microarray refers to microarray testing intended for postnatal and prenatal detection of constitutional chromosomal abnormalities, following ACMG standards and guidelines

Standards referenceACMG standards and guidelines (including the 2013 revision) provide technical and reporting recommendations for constitutional cytogenomic microarray analysis

Intended applicationsApplied as first‑tier postnatal testing for intellectual disability, autism spectrum disorders, and multiple congenital anomalies, and used in specific prenatal contexts

OpenPayer

Comparative Genomic Hybridization (CGH)

Coverage Criteria

Specified Covered Indications

Coding and Billing

Provider Actions and Administrative Guidance

Not Covered / Experimental Indications

Eligibility Requirements

Background and Definitions

Revision History