CurrentUnitedHealthcarePolicy CS017NE.F

Chromosome Microarray Testing (Non-Oncology Conditions) (for Nebraska Only)

Policy describes clinical indications, recommended use, and supporting evidence/guidance for chromosome microarray analysis (CMA) including aCGH and SNP array in prenatal, pediatric, and non-oncology diagnostic contexts; includes applicable diagnosis codes and professional society recommendations. This part (2 of 3) focuses on detailed indications, evidence summaries, and guideline endorsements for obstetric and pediatric uses.

Policy Summary

PayerUnitedHealthcare

PolicyChromosome Microarray Testing (Non-Oncology Conditions) (for Nebraska Only)

Policy CodePolicy CS017NE.F

Change TypeRevised diagnosis code list

Effective DateDec 1, 2025

Next Review Date

Key ActionObtain comprehensive pre-test genetic counseling and informed consent discussing benefits, limitations, potential VUS, incidental findings, non-paternity, consanguinity, and adult-onset conditions prior to ordering prenatal CMA.

POLICY UPDATE CHANGES

Updated list of applicable ICD-10 diagnosis codes to reflect annual edits.

15.3%CMA yield in fetuses with CHD

8.3%Karyotype yield in fetuses with CHD

49.9%Chromosome abnormalities in POC

2.5%pCNV yield in POC

Overall pathogenic/VUS in cohorts

55%Yield with co-existing CHD (selected cohort)

Coverage Summary

Policy subject: Chromosome microarray analysis (CMA) including array comparative genomic hybridization (aCGH) and SNP array for non-oncology conditions. Payer / geographic scope: UnitedHealthcare Medical Policy applicable to the State of Nebraska. High-level stance: mixed — the policy supports CMA as a first‑tier, medically necessary test for many prenatal and pediatric indications (e.g., fetuses with structural anomalies, stillbirth/POC, neurodevelopmental disorders) while deeming CMA unproven/not medically necessary for populations outside specified indications and noting limitations and consent requirements.

Policy identifiers and dates

Effective Date2025-12-01

Last Review2025-12-01

Policy NumberCS017NE.F

PayerUnitedHealthcare

Geographic ScopeNebraska

Coverage stancemixed

15.3%CMA diagnostic yield in fetuses with CHD (Lu et al. 2024)

9%CMA diagnostic yield in epilepsy (Sheidley et al. 2022)

49.9%Diagnostic yield for chromosomal abnormalities in POC (Peng et al. 2023)

Medical-Necessity Criteria

Clinical Indications and Considerations (narrative section)

Policy narrative summarizes situations where CMA is recommended or considered based on evidence and professional guidelines:

Prenatal diagnostic testing for fetuses with one or more major structural abnormalities identified on ultrasound (CMA recommended as first-tier test and may replace karyotype).

Supported by ACOG/SMFM (Practice Bulletin 162; 2016/2016b) and SMFM consults.

Prenatal diagnostic testing for fetuses with congenital heart defects (CHD), especially non-isolated CHD or septal defects (CMA recommended; higher diagnostic yield than karyotype).

Supported by multiple cohort studies and meta-analyses (Lu et al. 2024; Ye et al. 2024; Wang et al. 2023).

Prenatal testing for fetal growth restriction (FGR) or intrauterine growth restriction (IUGR) when accompanied by structural malformations or ultrasound soft markers (CMA increases diagnostic yield).

Supported by Li et al. (2025), Nguyen et al. (2025), SMFM guidance.

Provider Actions & Authorization

Prior Authorization

Prior Authorization / Specimen Requirement for Invasive Prenatal Testing

Invasive prenatal diagnostic specimen requirement: For invasive prenatal diagnostic procedures (e.g., amniocentesis, chorionic villus sampling, fetal tissue sampling), chromosome microarray analysis (CMA) requires submission of an appropriate invasive prenatal specimen. Prior authorization may be required by the plan before testing is performed; verify member benefits and obtain authorization when indicated.

Specimen types: amniotic fluid, chorionic villi, or fetal tissue obtained via invasive procedures.
Documentation: procedure note confirming invasive collection and gestational age when available.
Prior authorization: check plan-specific prior auth rules before sending specimen.

Prior Authorization

Check Plan Authorization & Billing Rules

Applicable Diagnosis Codes

Applicable ICD-10 Diagnosis Codes (listed in this part)ICD-10

Q93.2	Chromosome replaced with ring, dicentric or isochromosome.
Q93.3	Deletion of short arm of chromosome 4.
Q93.4	Deletion of short arm of chromosome 5.
Q93.7	Deletions with other complex rearrangements.
Q93.51	Angelman syndrome.
Q93.52	Phelan-McDermid syndrome.
Q93.59	Other deletions of part of a chromosome.
Q93.81	Velo-cardio-facial syndrome.
Q93.82	Williams syndrome.
Q93.88	Other microdeletions.

1–10 of 38

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Applicable ICD-10 codes (updated)ICD-10

Q89.89	Other congenital malformation syndromes, not elsewhere classified (added)
Q99.89	Other chromosomal abnormalities, not elsewhere classified (added)
QA0.0159	Code added (policy-specific) (added)
QA0.8	Code added (policy-specific) (added)
Q89.8	Other specified congenital malformations (removed)
Q99.8	Other specified chromosomal abnormalities (removed)

Background & Evidence Summary

Chromosome microarray analysis (aCGH and SNP array) is used to detect genome‑wide copy number variations and is more sensitive than karyotype for submicroscopic imbalances. The policy describes CMA as the recommended first‑tier test for many neurodevelopmental disorders (developmental delay/global developmental delay, intellectual disability, autism spectrum disorder) and for prenatal diagnostic evaluation when major fetal structural abnormalities are identified (and for stillbirth/POC analysis), while acknowledging limitations including inability to detect balanced rearrangements and that CMA can generate variants of uncertain significance (VUS) which may require parental segregation and further testing.

Study / Source	Key finding
Meta-analysis pooled proportion (CHD) (Wang et al., 2023)	Overall chromosome abnormalities 23%; aneuploidies 19%; 22q11 deletion 2%; other CNVs 4%
Mastromoro pooled incremental yield (cardiac anomalies)	Incremental diagnostic yield of CMA 5.79% overall; conotruncal 15.93%; TOF 11.28%
Srebniak fetal CMA results	1/119 (0.84%) clinically significant CNV for AMA/anxiety referrals; combined risk >1/180 for significant cytogenetic abnormality
Peng et al. (2023) meta-analysis	POC: diagnostic yields for chromosomal abnormalities 49.9% and pCNVs 2.5%; genomic disorders/syndromic pCNVs ~0.8%
Pasternak et al. (2020) / Prenatal termination cohort	Abnormal findings in 23.9% of terminated pregnancies; incremental yield of CMA 5.6% overall
Li et al. (2025) FGR cohort	Higher pCNV detection in FGR with structural malformations (19%) vs FGR with soft markers (1.5%) and isolated FGR (2.1%); multiple system malformations 60% vs single 6.3%
Nguyen et al. (2025) IUGR SNP-array study	SNP-based CMA detected >2x more genetic anomalies than karyotyping; 35% genetic abnormality detection in tested cases
Lu et al. (2024) CHD cohort	CMA diagnostic yield 15.3% vs karyotype 8.3%; higher detection in CHD with extracardiac anomalies (33.1% vs 9.9%)
Mastromoro et al. (2022c) meta-analysis (mixed anomalies)	CMA overall diagnostic yield 5.72% for mixed anomalies; higher yield for multiple structural anomalies (8.57%); VUS rate 2.86% for structural anomalies
Miclea et al. (2022) GDD/ID cohort	Pathogenic findings and VUS in 28% of participants; pCNVs/UPD in 18.5%
Harris et al. (2020) ASD toddlers	12.0% had pathogenic results among those who completed genetic testing; testing informed medical recommendations in most with pathogenic findings
McCormack et al. (2016) large cohort	In 5,369 subjects, 28% had deletion/duplication; 15.7% had VUS; microarray improved detection vs routine chromosome analysis
Sheidley et al. (2022) epilepsy meta-analysis	CMA diagnostic yield in epilepsy ~9% (lower than sequencing-based tests)

Nuchal Translucency (NT) measurement thresholds and incremental CMA yields

Isolated Nuchal Translucency (NT) threshold 1NT ≥ 2.5 mm (incremental CMA detection ~2.35%)

Isolated NT threshold 2NT ≥ 3.0 mm (incremental CMA detection ~3.89%)

Isolated NT threshold 3NT ≥ 3.5 mm (incremental CMA detection ~4.1%)

Context noteMastromoro meta-analysis shows increasing incremental CMA yield with larger NT measurements and recommends continued study to refine diagnostic algorithms

Revision History

12/01/2025revisedLatest

Updated list of applicable ICD-10 diagnosis codes to reflect annual edits: Added Q89.89, Q99.89, QA0.0159, and QA0.8; Removed Q89.8 and Q99.8. Archived previous policy version CS017NE.E.

Policy Summary

PayerUnitedHealthcare

PolicyChromosome Microarray Testing (Non-Oncology Conditions) (for Nebraska Only)

Policy CodePolicy CS017NE.F

Change TypeRevised diagnosis code list

Effective DateDec 1, 2025

Next Review Date

On This Page

Evaluation of stillbirth or intrauterine fetal death: CMA preferred over karyotype for higher success and detection rates.

Supported by ACOG/SMFM Obstetric Care Consensus (2020).

Products of conception (POC) testing following pregnancy loss: CMA provides higher informative results vs karyotype and identifies pCNVs; may be considered on case-by-case basis.

Supported by Peng et al. (2023) meta-analysis and Pauta et al. (2017).

Prenatal follow-up/confirmatory testing for abnormal noninvasive prenatal screening (NIPS) when small CNVs reported or discordant findings: CMA on CVS or amniocentesis may be used.

ACMG practice resource (Cherry et al., 2017).

Pediatric evaluation of neurodevelopmental disorders, global developmental delay (GDD), intellectual disability (ID), autism spectrum disorder (ASD), and congenital anomalies: CMA is recommended as a first-tier test for neurodevelopmental disability and congenital anomalies.

Supported by ACMG (Waggoner et al., 2018) and multiple pediatric studies (Miclea et al. 2022; Hayes 2023 summary).

Use of CMA is limited by inability to detect balanced rearrangements or some types of abnormalities; variants of uncertain significance (VUS) and need for parental segregation may require further testing.

Described limitations (ACMG guidance).

Indications consistent with professional guidelines (summarized evidence supporting first-tier use)

CMA is recommended as a first-tier test for individuals meeting any of the following clinical presentations, per cited professional organizations:

Individuals with developmental delay (DD), global developmental delay (GDD) or intellectual disability (ID).

ACMG, AAP, ISCA, CCMG, AAN cite CMA as first-line for these indications.

Individuals with autism spectrum disorder (ASD) when etiology is unknown (or per guideline-directed evaluation).

ACMG and other societies list CMA as first-tier for ASD.

Individuals with multiple congenital anomalies (MCA) or multiple major/minor congenital malformations not specific to a well-delineated syndrome.

ACMG/ISCA recommend CMA as first-line for congenital anomalies.

Prenatal cases with major fetal structural abnormalities when invasive diagnostic testing is planned and for evaluation of fetal loss/stillbirth when pursued.

ACMG technical standard and ACOG/SMFM references support prenatal CMA use.

Children/neonates with congenital heart defects (CHD) associated with DD or other malformations.

Multiple studies reported higher diagnostic yield of CNVs in CHD with comorbid DD/malformations.

Circumstances limiting value / considered investigational per AAN

Microarray testing may be considered investigational or of limited value when the following apply:

Absence of appropriate and informed consent from patient, parent, or guardian.

Inadequacy of knowledge about the test and actions required to address results.

When diagnosis of a disorder or syndrome is readily apparent based on clinical evaluation alone (targeted testing preferred).

When circumstances fall outside those delineated (i.e., lack of clear value), test considered investigational.

Pre-test targeted testing / metabolic evaluation expectations (per AAN/AACAP/ACMG)

Before CMA in some contexts, targeted evaluations are expected as applicable:

If warranted, biochemical testing for metabolic diseases has been performed and is negative.

Targeted genetic testing for a suspected syndrome (e.g., FMR1 for Fragile X) has been performed and is negative or not indicated.

Face-to-face genetic counseling provided and informed consent/assent obtained.

Policy-specific billing and authorization review: Providers must confirm UnitedHealthcare plan-specific requirements for CMA prior to ordering. Use the payer's provider portal or prior authorization tool to verify coverage, submission requirements, and whether a specific authorization form or diagnosis coding is required.

Verify member eligibility and benefits, including limits or exclusions for non-oncology CMA.
Use UnitedHealthcare online tools or contact provider services for prior auth status and required documentation.
Include clinical indications and relevant prior testing in authorization requests to avoid delays or denials.

Documentation Required

Pre-test Genetic Counseling & Informed Consent

Pre-test genetic counseling and informed consent: Pre-test genetic counseling is strongly recommended and should occur prior to ordering CMA. Counseling should cover test purpose, potential results (pathogenic, likely pathogenic, variants of uncertain significance, benign), limitations of the test, possible incidental findings, and implications for the patient and family. Document informed consent and counseling in the medical record prior to testing.

Document the counselor/clinician name, date of counseling, and that risks, benefits, and limitations were explained.
For prenatal testing, documentation should include discussion of possible outcomes and impact on pregnancy management.
Retain written informed consent when required by state law or institutional policy.

Billing Rule

When CMA May Replace Karyotype (Prenatal)

Replacement of karyotype in certain prenatal indications: CMA may replace karyotype for the evaluation of fetal structural anomalies or abnormal prenatal screening when higher-resolution genome-wide analysis is indicated. When CMA is performed in lieu of karyotype, document the clinical rationale and that the ordering clinician reviewed the trade-offs (e.g., CMA does not reliably detect balanced translocations or low-level mosaicism detectable by karyotype).

When CMA replaces karyotype, include documentation of ultrasound findings or other prenatal indications prompting genome-wide CMA.
If balanced rearrangement or suspected whole-chromosome aneuploidy remains a concern, consider concurrent karyotype or reflex testing per lab guidance.
Billing: follow payer guidance on when CMA is payable instead of or in addition to karyotype; include supporting clinical documentation with claims/authorization.

Documentation Required

Post-test Counseling & Parental Segregation

Post-test counseling and parental segregation testing: When CMA identifies a variant of uncertain significance (VUS) or a pathogenic/likely pathogenic copy number variant with unclear inheritance, arrange post-test genetic counseling and consider parental segregation testing to aid interpretation. Document counseling, family discussion, and any additional testing ordered.

Document counseling session content, recommendations, and patient decisions in the record.
Order parental testing when indicated to determine de novo vs inherited status; include this plan in the authorization/claim if required.
Provide clear communication about the potential need for reclassification of VUS over time and possible result updates.

Documentation Required

CMA for Stillbirth / Products of Conception

Use of CMA in stillbirth and products of conception (POC): CMA is appropriate for evaluation of intrauterine fetal demise, stillbirth, and products of conception when genetic etiology is suspected. Ensure specimen source, collection method, and adequate tissue quality are documented. Prior authorization may be required per plan.

Preferred specimens: fetal tissue or products of conception with documented fetal origin; placental tissue may be used if fetal tissue is not available but note potential maternal cell contamination.
Include pathology or obstetric operative notes confirming specimen source and handling to support medical necessity.
Document gestational age and relevant clinical history (e.g., recurrent pregnancy loss) when requesting CMA for POC.

Documentation Required

Prior Targeted Testing / Metabolic Evaluation When Indicated

Targeted testing and metabolic evaluation before CMA when indicated: For certain presentations (e.g., suspected single-gene disorder, metabolic disease, or a clinically recognizable syndrome), targeted genetic testing or biochemical/metabolic evaluation should be performed first. Document prior targeted testing or metabolic workup and rationale for proceeding to CMA if those tests were non-diagnostic.

Provide results and dates of prior targeted molecular tests or metabolic studies in the authorization request.
If targeted testing is negative or not indicated, document why genome-wide CMA is the appropriate next step.
Failure to document prior testing when clinically appropriate may result in claim denial or request for additional information.