UnitedHealthcare Chromosome Microarray Coverage Update

Coverage Criteria

Medically Necessary Indications

Covered when the test is used for ANY of the following:

Prenatal/fetal indications: Evaluation of an embryo or fetus in any of the following situations: intrauterine fetal demise or stillbirth; testing products of conception following pregnancy loss; or individuals undergoing invasive prenatal diagnostic testing (amniocentesis, chorionic villus sampling, or fetal tissue sampling).

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Postnatal neurodevelopmental indications: Evaluation of individuals with one or more of the following: autism spectrum disorder (ASD); isolated severe congenital heart disease; multiple congenital anomalies not specific to a well-delineated genetic syndrome and not identifiable by clinical evaluation alone; or developmental delay/intellectual disability when a specific genetic syndrome is not suspected.

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Familial follow-up: Evaluation of a biological parent or sibling of a fetus or child who has an abnormal or equivocal chromosome microarray testing result to determine inheritance and aid interpretation.

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Not Medically Necessary

Not medically necessary: Chromosome microarray testing (aCGH or SNP array) is unproven and not medically necessary for populations and conditions other than those explicitly listed as proven and medically necessary due to insufficient evidence of efficacy.

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General indications and test characteristics

Clinical rationale and general indications

General clinical indications for CMA: Chromosome microarray analysis (CMA; aCGH and/or SNP array) detects copy number variations (deletions and duplications) across the genome and is more sensitive than conventional karyotype or FISH for submicroscopic imbalance. CMA is used for diagnosing chromosomal abnormalities in fetuses, neonates, and children with developmental disorders; it may be targeted to syndrome-associated regions or genome-wide. Limitations include detection of variants of uncertain significance and inability to detect balanced rearrangements.

From descriptive sections on CMA utility and limitations

Prenatal high-yield indications

Evidence from recent obstetric studies supporting use of CMA in specific prenatal scenarios

Prenatal situations with demonstrated higher diagnostic yield: Recent studies demonstrate increased diagnostic yield for CMA compared with karyotype in fetuses with: structural malformations (higher yield when multiple organ systems are involved), congenital heart defects (particularly CHD with extracardiac anomalies and certain subtypes such as conotruncal defects/TOF), and fetal growth restriction/intrauterine growth restriction when associated with structural malformations; CMA detected substantially more pathogenic CNVs in these cohorts (examples: Li et al. FGR: pCNV rates 19% vs 1.5% vs 2.1% across FGR subgroups; Nguyen et al.: 35% genetic abnormality detection in IUGR with malformations; Lu et al.: 15.3% CMA vs 8.3% karyotype in CHD).

Study results: Li et al.; Nguyen et al.; Lu et al.

Indications supported by professional societies

Covered when ALL of the following are met (per professional society guidance):

Prenatal structural anomaly: CMA is recommended as the primary test for patients undergoing prenatal diagnosis when one or more major fetal structural abnormalities are identified on ultrasound and invasive diagnostic testing is performed; CMA can replace conventional fetal karyotype in this setting.

ACOG/SMFM: CMA primary test for fetal structural abnormalities

Stillbirth or intrauterine fetal death: CMA of fetal tissue (amniotic fluid, placenta, or products of conception) is recommended in the evaluation of stillbirth/intrauterine fetal demise when cytogenetic analysis is desired because CMA has higher likelihood of obtaining results and improved detection compared with karyotype.

ACOG/SMFM consensus: preferred method for stillbirth evaluation.

Abnormal or discordant NIPS or small CNV on NIPS: CMA on CVS or amniocentesis may be used for confirmatory diagnosis for abnormal noninvasive prenatal screening (NIPS) results and should be used to follow-up small copy number changes reported as positive on NIPS; CMA can be performed as a reflex to karyotype when indicated.

Covered indications

Covered when meeting professional society‑recommended indications

Prenatal indications: CMA is covered when invasive prenatal diagnostic testing is performed for fetal major structural anomalies, stillbirth, unexplained early-onset fetal growth restriction (especially <32 weeks), multiple fetal malformations, or increased nuchal translucency; CMA may replace karyotype in these scenarios per society guidance.

Supported by SMFM, SOGC/CCMG, and ACMG guidance

Pediatric neurodevelopmental indications: CMA is covered as a first-tier diagnostic test for individuals with developmental delay/intellectual disability (DD/ID), global developmental delay (GDD), autism spectrum disorder (ASD), or multiple congenital anomalies not specific to a well-delineated genetic syndrome.

Supported by ACMG, AAP, ISCA, CCMG

When targeted testing precedes CMA: If a specific recognized genetic syndrome is strongly suspected (for example Fragile X, PTEN-related conditions, Rett), targeted syndrome-specific testing is recommended first; if targeted testing is negative or nondiagnostic, CMA is appropriate as the next step.

Per CCMG/AACAP and other societies

Guideline-aligned coverage criteria

Coverage aligned with professional guidance:

CMA first-tier for neurodevelopmental disorders/congenital anomalies: CMA is recommended as a first-tier diagnostic test for individuals with developmental disabilities, global developmental delay (GDD), intellectual disability (ID), or autism spectrum disorder (ASD), and for individuals with congenital anomalies or structural fetal anomalies detected prenatally; follow-up targeted testing or sequencing may be considered if CMA is non-diagnostic.

Supported by ISCA/ACMG consensus and CCMG position statement

Fragile X testing is advised when family history or clinical features are suggestive of fragile X syndrome and should be performed as appropriate prior to or concurrent with CMA per society guidance.

CCMG reference

Second-tier testing: When CMA is negative or non-diagnostic and a monogenic disorder is suspected by phenotype, consider whole exome sequencing (WES) or comprehensive gene panels as second‑tier testing per professional recommendations.

CCMG and other societies recommend WES/panels as second-tier

Use of chromosome microarray testing (CMA) is limited to the specific clinical indications listed in this policy. CMA using array comparative genomic hybridization (aCGH) and/or single‑nucleotide polymorphism (SNP) array is considered proven and medically necessary only for the prenatal and postnatal indications described in the covered indications section (for example: intrauterine fetal demise/stillbirth, products of conception after pregnancy loss, invasive prenatal diagnostic samples, ASD, isolated severe congenital heart disease, multiple anomalies not attributable to a well‑delineated syndrome, developmental delay/intellectual disability when a specific syndrome is not suspected, and familial follow‑up after an abnormal/equivocal result). CMA for populations or conditions not explicitly listed in those covered indications is considered unproven and not medically necessary.

Chromosome microarray testing (aCGH and SNP array) detects copy number variations (deletions and duplications) across the genome and has greater sensitivity than conventional karyotype for submicroscopic imbalances. However, CMA has important technical limitations: it may detect variants of uncertain significance and false positive findings that require additional testing, and CMA cannot detect balanced chromosomal rearrangements or other abnormalities where there is no net gain or loss of chromosomal material; additional or alternative testing (e.g., karyotype, FISH, or targeted assays) may be required in those situations.

Professional society guidance notes that CMA is not recommended as a first‑line test to evaluate first‑trimester pregnancy losses because available data are limited. For first‑trimester products of conception, CMA may be considered on a case‑by‑case basis but is not the routine initial diagnostic approach in early pregnancy loss.

CMA would not be considered medically necessary when a diagnosis is readily apparent from clinical evaluation alone or when testing is performed without adequate informed consent and understanding of the test limitations and implications. Lack of appropriate informed consent or clinical circumstances that make test results unlikely to alter management may limit the clinical value of CMA.

The Canadian College of Medical Genetics (CCMG) position states that CMA is a first‑tier test for individuals with global developmental delay, intellectual disability, or autism spectrum disorder, but CCMG does not recommend routine genetic testing for individuals with neurodevelopmental concerns when GDD, ID, or ASD are not present unless the clinical phenotype suggests a recognizable syndromic etiology or an inherited metabolic disease.

All other populations and clinical scenarios that are not specifically enumerated as covered indications in this policy are considered unproven and not medically necessary for CMA because evidence of clinical utility and impact on management is insufficient.

The potential detection of a variant of uncertain significance (VUS), or findings that require follow‑up testing, are recognized limitations of CMA. Such findings alone do not, by themselves, define a test as non‑covered; rather, interpretation and follow‑up (including parental testing or confirmatory cytogenetic studies) are required to determine clinical significance and appropriate management.

As noted by SMFM and other professional bodies, routine use of CMA for first‑trimester pregnancy loss is not recommended due to limited evidence. In addition, CMA may be considered investigational or of limited value when used outside of the specific, guideline‑supported indications described in this policy.

Genetic testing, including CMA, is not generally recommended for neurodevelopmental presentations when global developmental delay (GDD), intellectual disability (ID), or autism spectrum disorder (ASD) are absent, unless the individual’s phenotype or family history indicates a syndromic or inherited metabolic cause that warrants targeted testing or further genetic evaluation.

Covered Indications

Prenatal/fetal evaluation including intrauterine fetal demise or stillbirth, products of conception after pregnancy loss, and invasive prenatal testing samples.

Postnatal evaluation for ASD, isolated severe congenital heart disease, multiple anomalies not specific to a well-delineated genetic syndrome, developmental delay/intellectual disability when a specific syndrome is not suspected.

Evaluation of a biological parent or sibling following an abnormal or equivocal CMA result in a fetus or child.

Prenatal diagnosis for fetuses with structural malformations, congenital heart defects (especially with extracardiac anomalies), and fetal growth restriction or IUGR when abnormalities are identified on ultrasound.

Coding and Diagnosis Codes

Covered CPT/HCPCS CodesmixedCovered

0156U	Copy number (e.g., intellectual disability, dysmorphology), sequence analysis.
0209U	Cytogenomic constitutional (genome-wide) analysis, interrogation of genomic regions for copy number, structural changes and areas of homozygosity for chromosomal abnormalities.
81228	Cytogenomic (genome-wide) analysis for constitutional chromosomal abnormalities; interrogation of genomic regions for copy number variants, comparative genomic hybridization [CGH] microarray analysis.
81229	Cytogenomic (genome-wide) analysis for constitutional chromosomal abnormalities; interrogation of genomic regions for copy number and single nucleotide polymorphism (SNP) variants, comparative genomic hybridization (CGH) microarray analysis.
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.
81479	Unlisted molecular pathology procedure
S3870	Comparative genomic hybridization (CGH) microarray testing for developmental delay, autism spectrum disorder and/or intellectual disability

Relevant ICD-10 Diagnosis Codes (partial list)ICD-10

F70	Mild intellectual disabilities.
F71	Moderate intellectual disabilities.
F72	Severe intellectual disabilities.
F73	Profound intellectual disabilities.
F79	Unspecified intellectual disabilities.
F84.0	Autistic disorder.

Pregnancy/prenatal ICD-10 Codes (partial group)ICD-10

O02.1	Missed abortion.
O03.4	Incomplete spontaneous abortion without complication.
O03.9	Complete or unspecified spontaneous abortion without complication.
O35.10X0	Maternal care for (suspected) chromosomal abnormality in fetus, unspecified, not applicable or unspecified.
O35.11X- O35.19X	Series of codes for maternal care for suspected specific chromosomal abnormalities in fetus (Trisomy 13/18/21, Turner, sex chromosome abnormalities, other chromosomal abnormalities).

Applicable ICD-10-CM Codes (maternal/fetal indications and congenital anomalies list partial)ICD-10

O35.13X9	Maternal care for (suspected) chromosomal abnormality in fetus, Trisomy 21, other fetus
O35.14X0	Maternal care for (suspected) chromosomal abnormality in fetus, Turner Syndrome, not applicable or unspecified
O35.14X1	Maternal care for (suspected) chromosomal abnormality in fetus, Turner Syndrome, fetus 1
O35.14X2	Maternal care for (suspected) chromosomal abnormality in fetus, Turner Syndrome, fetus 2
O35.14X3	Maternal care for (suspected) chromosomal abnormality in fetus, Turner Syndrome, fetus 3
O35.14X4	Maternal care for (suspected) chromosomal abnormality in fetus, Turner Syndrome, fetus 4
O35.14X5	Maternal care for (suspected) chromosomal abnormality in fetus, Turner Syndrome, fetus 5
O35.14X9	Maternal care for (suspected) chromosomal abnormality in fetus, Turner Syndrome, other fetus
O35.15X0	Maternal care for (suspected) chromosomal abnormality in fetus, sex chromosome abnormality, not applicable or unspecified
O35.15X2	Maternal care for (suspected) chromosomal abnormality in fetus, sex chromosome abnormality, fetus 2

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Applicable ICD-10-CM Codes (congenital heart and chromosomal conditions)ICD-10

O36.4XX0	Maternal care for intrauterine death, not applicable or unspecified
P02.9	Newborn affected by abnormality of membranes, unspecified
P95	Stillbirth
Q20.1	Double outlet right ventricle
Q21.0	Ventricular septal defect
Q21.11	Secundum atrial septal defect
Q21.12	Patent foramen ovale
Q21.13	Coronary sinus atrial septal defect
Q21.14	Superior sinus venosus atrial septal defect
Q21.15	Inferior sinus venosus atrial septal defect

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Additional ICD-10-CM Codes (neurodevelopmental and screening)ICD-10

Q93.81	Velo-cardio-facial syndrome
Q93.82	Williams syndrome
Q93.88	Other microdeletions
Q99.89	Other specified chromosome abnormalities
Q99.9	Chromosomal abnormality, unspecified
QA0.0159	Neurodevelopmental disorder, related to other genes associated with transcription and gene expression
R62.0	Delayed milestone in childhood
R62.51	Failure to thrive (child)
Z36.0	Encounter for antenatal screening for chromosomal anomalies
Z87.74	Personal history of (corrected) congenital malformations of heart and circulatory system

Covered CPT CodesCPT

No codes listed

Applicable ICD-10 diagnosis code edits (annual update)ICD-10

Q89.89	ICD-10 code added (listed in policy history)
Q99.89	ICD-10 code added (listed in policy history)
QA0.0159	ICD-10 code added (listed in policy history)
QA0.8	ICD-10 code added (listed in policy history)
Q89.8	ICD-10 code removed (listed in policy history)
Q99.8	ICD-10 code removed (listed in policy history)

Diagnostic yield metrics

CMA diagnostic yield for fetal congenital heart defects (Lu et al., 2024)15.3% (CMA) vs 8.3% (karyotype) in a 642-case single-center CHD cohort

Pathogenic CNV detection in FGR with structural malformations (Li et al., 2025)19% pCNV detection rate in FGR with structural malformations vs 1.5% with ultrasound soft markers vs 2.1% isolated FGR

Proportion of genetic abnormalities in IUGR with malformations (Nguyen et al., 2025)35% genetic abnormality detection among tested IUGR cases (SNP array + karyotype subgroup)

Overall incremental CMA yield in mixed fetal anomalies (systematic review)Reported pooled incremental yields vary; individual study yields include ~5.72% for mixed fetal anomalies (Mastromoro et al.)

Provider Actions and Requirements

Prior Authorization

Prior authorization may be required for certain chromosome microarray analysis (CMA) procedure codes depending on the member's benefit plan. Verify plan-specific prior authorization (PA) rules and obtain PA when required before ordering testing to avoid claim denials.

Check the member's benefit contract for plan-specific PA requirements prior to ordering CMA.
If PA is required, submit clinical documentation supporting the medical indication listed in this policy.

Documentation Required

Pre-test Genetic Counseling and Consent

Genetic counseling is strongly recommended and typically expected prior to CMA. Counseling should include discussion of test benefits, limitations, possible results (pathogenic, benign, VUS), implications (including potential non-paternity, consanguinity, adult-onset findings), and alternatives. Document that counseling was provided or offered.

Offer and document pre-test genetic counseling by a trained genetics professional or other provider with genetics expertise.

Eligibility Requirements

Top-level eligibility requirements for CMA ordering and coverage are defined by the clinical indications and documentation expectations in this policy; documentation should support a covered indication and evidence that informed consent and genetic counseling were provided when appropriate.

When CMA identifies a copy number variant of uncertain significance or a pathogenic CNV, parental testing is recommended to determine whether the variant is inherited or de novo. Parental studies assist interpretation and can directly affect clinical counseling and management.

Additional eligibility criteria are governed by the covered indications and documentation requirements described elsewhere in this policy; no separate top‑level family history requirement is mandated beyond those clinical criteria.

No additional standalone eligibility nodes are specified; ordering should follow the clinical indications and counseling/documentation recommendations provided in this policy.

Providers should ensure that clinical documentation supports the indication for testing and that counseling and consent have been addressed per policy guidance.

There are no further top‑level eligibility statements beyond the covered indications, counseling expectations, and documentation requirements already described.

Clinical context, including who ordered the test and the documented indication, should be recorded in the medical record to support coverage decisions.

Not Covered / Limitations

Chromosome microarray testing (aCGH or SNP array) performed for any indication other than those explicitly listed as covered in this policy is considered not medically necessary and investigational due to insufficient evidence of clinical benefit.

Balanced chromosomal rearrangements are not detectable by CMA because these rearrangements do not result in net gain or loss of chromosomal material; therefore, CMA will not identify balanced translocations or inversions and is not an appropriate test when detection of balanced rearrangements is required.

Because available data are limited, CMA is not recommended as the first‑line test for evaluation of first‑trimester pregnancy losses; professional guidance advises against routine first‑line use in this specific early pregnancy context.

CMA performed for clinical situations that fall outside the delineated, guideline‑supported indications (for example, routine screening in populations without the described prenatal or postnatal findings) is considered investigational or of limited clinical value and therefore not covered.

Genetic testing for neurodevelopmental disorders is not generally indicated when GDD, ID, or ASD are absent unless the clinical phenotype or family history suggests a syndromic etiology or an inherited metabolic disease; such testing in those circumstances is considered not covered.

Background

Chromosome microarray testing (aCGH and SNP array) is a genomic assay that identifies copy number variants (deletions and duplications) across the genome. CMA includes array comparative genomic hybridization (aCGH) and single‑nucleotide polymorphism (SNP) array platforms. It is more sensitive than conventional karyotype for submicroscopic CNVs and is widely used prenatally (from invasive samples and products of conception) and postnatally for evaluation of developmental disorders, congenital anomalies, and neurodevelopmental conditions. CMA requires invasive sampling for diagnostic prenatal testing (e.g., amniocentesis or CVS) and may be performed as targeted or genome‑wide analysis depending on the clinical question.

Definitions

Developmental Delay

DefinitionDevelopmental Delay: may be used to describe children younger than 5 years who present with delays in attainment of developmental milestones at the expected age.

Age contextTypically applied to children under age 5 for delays in motor, language, social, or cognitive milestones.

Clinical useUsed as an indication for diagnostic evaluation including CMA when delays are significant and no specific syndrome is suspected.

Intellectual Disability

DefinitionIntellectual Disability: a condition diagnosed before age 18 that includes below-average intellectual function and lack of skills necessary for daily living.

OnsetDiagnosis is made before age 18.

Revision History

2025-11-01ICD-10 code editsLatest

Updated applicable ICD-10 diagnosis codes: added Q89.89, Q99.89, QA0.0159, and QA0.8; removed Q89.8 and Q99.8.

This policy provides standard benefit plan interpretation and does not substitute for plan‑specific rules. Check federal, state, or contractual plan documents for any prior authorization requirements that may apply to CMA codes before ordering; plan‑level prior authorization rules may differ from the coverage guidance in this policy.

OpenPayer

Chromosome Microarray Testing (Non-Oncology Conditions) (For New Mexico Only)

Coverage Criteria

Covered Indications

Coding and Diagnosis Codes

Provider Actions and Requirements

Eligibility Requirements

Not Covered / Limitations

Background

Definitions

Revision History