Chromosome Microarray Testing (Non-Oncology Conditions) - North Carolina

Coverage Summary

UnitedHealthcare medical policy (North Carolina only) defines clinical indications where chromosome microarray testing (CMA) using aCGH and/or SNP array is considered medically necessary for listed prenatal and pediatric indications and not medically necessary for all other indications. The policy applies only to the state of North Carolina and is effective 2026-01-01.

High-level scope: CMA is supported as a first-tier diagnostic test for specified prenatal/fetal evaluations (including intrauterine fetal demise/stillbirth, testing products of conception after pregnancy loss, and invasive prenatal testing) and postnatal/pediatric evaluations (including developmental delay/intellectual disability, autism spectrum disorder, isolated severe congenital heart disease, and multiple anomalies not specific to a well-delineated genetic syndrome). CMA is also indicated for testing biological parents or siblings to clarify an abnormal or equivocal CMA result in a fetus or child. All other indications are considered unproven or not medically necessary per the policy.

Medical-Necessity Criteria

Medically Necessary Indications

Chromosome microarray testing using aCGH and/or SNP array is proven and medically necessary for the following:

Prenatal / Fetal evaluation

Intrauterine Fetal Demise or Stillbirth
Testing the products of conception following pregnancy loss
Individuals undergoing invasive prenatal testing (i.e., amniocentesis, chorionic villus sampling, or fetal tissue sampling)

Postnatal / Pediatric evaluation

Autism spectrum disorder (ASD)
Isolated severe congenital heart disease
Multiple anomalies that are not specific to a Well-Delineated Genetic Syndrome and cannot be identified by a clinical evaluation alone
Developmental Delay/Intellectual Disability where a specific syndrome is not suspected

Family member testing

Evaluation of biological parent or sibling of a fetus or child with an abnormal or equivocal finding on chromosome microarray testing results

General indications where CMA is recommended as first-tier/primary test

CMA is recommended as a first-tier diagnostic test when ALL of the following apply:

General first-tier criteria

Individual with unexplained developmental delay (DD), global developmental delay (GDD), or intellectual disability (ID)
Autism spectrum disorder (ASD) when ID/GDD or syndromic features present; CMA is a first-tier test for ASD evaluation
Multiple congenital anomalies not specific to a well-delineated genetic syndrome
Prenatal fetal structural abnormality identified on ultrasound and invasive prenatal diagnostic testing (e.g., amniocentesis or CVS) is being performed

Obstetric / Prenatal uses

CMA is recommended in these prenatal contexts when ANY of the following are present:

Prenatal scenarios

Fetus with one or more major structural abnormalities on ultrasound and undergoing invasive prenatal diagnosis
ACOG/ACMG recommend CMA as primary test for structural abnormalities
Stillbirth or intrauterine fetal death when further cytogenetic analysis is desired (CMA preferred over karyotype for nonviable tissue)
ACOG/SMFM state microarray preferred for stillbirth
Prenatal diagnostic testing for fetal growth restriction (FGR) with fetal malformation, polyhydramnios, or both; or unexplained isolated FGR diagnosed < 32 weeks when associated findings present
SMFM recommends offering CMA in these FGR contexts
Follow-up/confirmatory testing for abnormal noninvasive prenatal screening (NIPS) results or when small copy number changes are reported on NIPS; CMA may be used for confirmatory diagnosis on CVS or amniocentesis

Pediatrics uses

CMA is recommended or appropriate when ALL of the following apply in pediatric patients:

Pediatric first-tier contexts

Child with unexplained GDD/ID or developmental delay
AAP/AACAP recommend CMA as first-line for ID/GDD
Child with ASD (CMA is common first-tier test), especially when comorbid ID, syndromic features, or facial dysmorphism
Hayes and professional guidelines cite CMA as common first-tier for ASD when features present
Children with congenital heart defects (CHD) especially when associated with other anomalies or developmental concerns
Studies show higher yield in CHD with extracardiac anomalies; CMA recommended particularly for non-isolated CHD

Neurology / Epilepsy

Use of CMA in epilepsy evaluation is considered when:

Epilepsy evaluation scenarios

Child with epilepsy particularly when comorbid developmental and epileptic encephalopathy or neurodevelopmental conditions
Sheidley meta-analysis: higher yield when developmental comorbidities present
CMA may be used alongside epilepsy gene panels and whole exome/genome sequencing; CMA has lower diagnostic yield for epilepsy compared to sequencing
Sheidley: CMA yield ~9% vs higher yields for sequencing

Situations limiting value of CMA (investigational/not medically necessary)

CMA is NOT considered medically necessary when ANY of the following apply:

Situations limiting value of CMA

Diagnosis of a disorder or syndrome is readily apparent based on clinical evaluation alone (targeted testing preferred)
AAN/AACAP guidance notes targeted testing preferred when syndrome recognized
Lack of informed consent or absence of appropriate pretest counseling
AAN and policy require informed consent and pretest counseling
When the test result would not have potential to impact clinical management
AAN states lack of clear value when results won't impact management
Use of CMA as first-line test for first trimester pregnancy losses is not routinely recommended due to limited data

Not Medically Necessary / Unproven Indications

Chromosome microarray testing using aCGH or SNP array is unproven and not medically necessary for all other populations and conditions.

Unlisted indications: Any indication not listed in the Medically Necessary Indications section

CMA considered unproven/not medically necessary for all other populations and conditions

Coding

Covered / Applicable Procedure Codes (reference list)mixed

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

ICD-10 Diagnosis Codes Mentioned (reference list)ICD-10

F70	Mild intellectual disabilities
F71	Moderate intellectual disabilities
F72	Severe intellectual disabilities
F73	Profound intellectual disabilities
F78.A1	SYNGAP1-related intellectual disability
F78.A9	Other genetic related intellectual disability
F79	Unspecified intellectual disabilities
F80.0	Phonological disorder
F80.1	Expressive language disorder
F80.2	Mixed receptive-expressive language disorder

1–10 of 195

1/20

ICD-10 diagnosis codes updated (annual edits)ICD-10

Q89.89	added
Q99.89	added
QA0.0159	added
QA0.8	added
Q89.8	removed
Q99.8	removed

Provider Actions & Administrative Requirements

Documentation Required

Pre-test genetic counseling recommended

Pre-test genetic counseling is strongly recommended to inform the person being tested (or the pregnant individual/couple) about the benefits, limitations, possible outcomes, and implications of chromosome microarray testing prior to ordering the test.

Documentation Required

Invasive prenatal sample requirement for diagnostic prenatal CMA

For diagnostic prenatal chromosome microarray analysis, results must be obtained from an invasive prenatal sample collected via amniocentesis or chorionic villus sampling (CVS) per laboratory/ACMG guidance. Do not rely on noninvasive screening samples for diagnostic CMA.

Background & Evidence

Chromosome microarray analysis (CMA), including array comparative genomic hybridization (aCGH) and single-nucleotide polymorphism (SNP) array, detects genomic copy number variations (CNVs) such as deletions and duplications across the genome and generally has a higher diagnostic yield than karyotype for many prenatal and pediatric indications. CMA analyzes multiple DNA sequences simultaneously and may be genome-wide or targeted to known syndrome-associated regions.

Limitations: CMA cannot detect balanced rearrangements (where there is no net gain or loss of chromosomal material), may identify variants of uncertain significance (VUS) that require further interpretation (for example parental testing), and can produce false positives that necessitate confirmatory testing. Pre-test genetic counseling is strongly recommended to discuss these advantages and limitations.

Evidence / Source	Key finding
Diagnostic yield examples (selected studies described)	CMA yield varies by indication; example: 15.3% diagnostic yield in fetal CHD series (Lu et al. 2024); POC meta-analysis: chromosomal abnormalities 49.9% and pCNVs 2.5% (Peng et al. 2023); variable incremental yields for increased nuchal translucency and structural anomalies.
Maya et al. 2018	High-penetrance CNV frequency: 0.1% in low-risk prenatal, 0.9% in high-risk prenatal, and 2.6% postnatal based on 21,594 CMAs.
Pauta et al. 2017	In early pregnancy loss (≤20 weeks) CMA provided informative results in 95% of cases vs 67% for karyotyping and a 2% greater pCNV yield.
McCormack 2016	In 5,369 pre/postnatal subjects, 28% had deletions/duplications; 15.7% had variants of uncertain significance (VUS).
Jang 2019	Among 617 participants with DD/ID/ASD/MCA, 19.8% had abnormal CMA; results influenced clinical management in 71.4% of those tested.
ACMG consensus	Consensus (Miller et al. 2010) and subsequent ACMG guidance: CMA is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies; CMA recommended for prenatal cases with major structural anomalies and for stillbirth evaluation.
Technical standard	ACMG 2021 technical standard (Shao L et al. 2021) affirms CMA (array CGH and SNP array) as well-accepted for constitutional chromosomal imbalance detection and as first-tier for multiple congenital anomalies, autism, and/or intellectual disability.

Definitions

Definitions used in this policy:

Developmental Delay: May be used to describe children younger than 5 years who present with delays in attainment of developmental milestones.

Source definition

Intellectual Disability:

Revision History & Policy Updates

2026-01-01code_additionLatest

Annual ICD-10 code edits effective 01/01/2026: Added ICD-10 diagnosis codes Q89.89, Q99.89, QA0.0159, and QA0.8 to the list of applicable diagnosis codes.

2026-01-01code_removalLatest

Annual ICD-10 code edits effective 01/01/2026: Removed ICD-10 diagnosis codes Q89.8 and Q99.8 from the list of applicable diagnosis codes.

2026-01-01administrative