Is prenatal carrier screening for cystic fibrosis, spinal muscular atrophy, and hemoglobinopathies, as well as aneuploidy testing and 22Q11.2 deletion testing, medically indicated for a 32-year-old pregnant female with a singleton pregnancy and no relevant medical history?

Medical Necessity Determination for Prenatal Genetic Testing

Direct Recommendation

The requested carrier screening panel (ASPA, CFTR, GBA, HEXA, IKBKAP genes) is medically necessary and should be approved, as it meets established criteria for prenatal carrier screening in a pregnant patient. However, the aneuploidy testing (81420) and 22q11.2 deletion testing should be approved with the understanding that 22q11.2 deletion screening has conditional support, while broader microdeletion panels beyond 22q11.2 remain investigational. 1

Carrier Screening Analysis (CPT 81200,81220,81251,81255,81260)

Meets Medical Necessity Criteria

This carrier screening panel is medically necessary because it includes cystic fibrosis (CFTR) and tests for conditions with established clinical utility in prenatal screening. 1

• The American College of Medical Genetics (ACMG) 2024 guidelines explicitly state that expanded carrier screening panels must include cystic fibrosis (CF) and spinal muscular atrophy (SMA) for all individuals who are pregnant or planning pregnancy 1
• The requested panel includes CFTR (cystic fibrosis) gene testing, which satisfies the mandatory CF screening requirement 1
• Results will be used for pregnancy management and family planning, meeting the second criterion for medical necessity 1

Panel Components Justified

The specific genes requested represent conditions with significant carrier frequencies in certain populations:

• CFTR (81220): Universal screening recommended for all pregnant women regardless of ethnicity 1, 2
• HEXA (81255): Screening for Tay-Sachs disease, particularly relevant for Ashkenazi Jewish ancestry 1
• GBA (81251): Gaucher disease screening, relevant for Ashkenazi Jewish populations 1
• ASPA (81200): Canavan disease screening, relevant for Ashkenazi Jewish populations 1
• IKBKAP (81260): Familial dysautonomia screening, relevant for Ashkenazi Jewish populations 1

ACMG Tier Classification

The ACMG recommends that all pregnant patients should be offered tier 3 carrier screening, which includes 97 autosomal recessive genes and 16 X-linked genes. 1 The requested panel represents a subset of conditions that fall within tier 1-3 recommendations, making it clinically appropriate even if the full tier 3 panel is not being ordered.

Critical Caveat Regarding SMN1

The insurance policy correctly notes uncertainty about whether SMN1 (spinal muscular atrophy) is included in this panel. 1 The ACMG 2024 guidelines explicitly require that carrier screening panels include SMA alongside CF 1. If this facility's panel does not include SMN1, the provider should be informed that additional SMA carrier screening should be offered separately to meet current standards of care.

Aneuploidy Testing Analysis (CPT 81420)

22q11.2 Deletion Testing - Conditionally Approved

ACMG suggests that NIPS for 22q11.2 deletion syndrome be offered to all patients, though this is a conditional rather than strong recommendation. 1

• This represents a conditional recommendation based on moderate certainty of evidence 1
• The 22q11.2 deletion syndrome is the most common pathogenic microdeletion identified prenatally, with prevalence of 1 in 990 to 1 in 2,148 1
• In a prospective study of 18,289 pregnancies, sensitivity was 83% (10 of 12 cases detected) with a positive predictive value of 52.6% 1
• The false positive rate was only 0.05% 1

Broader Microdeletion Screening - Investigational

The insurance policy is correct that broader microdeletion/microduplication screening beyond 22q11.2 remains investigational. 1

• ACMG evidence demonstrates that sensitivity and specificity of CNV screening in general is below that of common trisomies 1
• Genome-wide approaches for rare autosomal trisomies and multiple microdeletion syndromes have not established clinical utility 1

Standard Aneuploidy Screening (Trisomy 21,18,13)

If the 81420 code includes standard cell-free DNA screening for trisomies 21,18, and 13:

• ACMG strongly recommends NIPS over traditional screening methods for trisomy screening in singleton pregnancies 1, 3
• Sensitivity for trisomy 21 is >99% with specificity >99.9% 1
• This represents a strong recommendation based on high certainty of evidence 1

Approval Recommendation Algorithm

Step 1: Approve Carrier Screening Panel

• CPT codes 81200,81220,81251,81255,81260 should be approved as medically necessary 1
• Meets criteria: pregnant patient, panel includes required CF screening, results will guide pregnancy management 1

Step 2: Verify SMN1 Inclusion

• Confirm whether the facility's panel includes SMN1 testing 1
• If not included, recommend separate SMA carrier screening be offered 1

Step 3: Aneuploidy Testing Decision

• If 81420 includes standard trisomy 21/18/13 screening: approve as strongly recommended 1
• If 81420 includes 22q11.2 deletion testing: approve with conditional support, ensure appropriate pre-test counseling about limitations 1
• If 81420 includes broader microdeletion panel beyond 22q11.2: deny as investigational per policy and ACMG evidence 1

Step 4: Documentation Requirements

• Confirm singleton pregnancy (NIPS performance differs in multiples) 1, 3
• Verify gestational age >10 weeks for cell-free DNA testing 3
• Document that patient has received appropriate genetic counseling 1

Common Pitfalls to Avoid

Do not deny the entire request based on the 22q11.2 component alone - the carrier screening panel clearly meets medical necessity criteria and should be approved separately from the aneuploidy testing decision 1

Ensure the patient understands that positive NIPS results require confirmatory diagnostic testing (amniocentesis or CVS) before making irreversible decisions 1, 3

Verify that both partners will be tested if the patient is found to be a carrier - this is essential for accurate risk assessment for autosomal recessive conditions 1

Confirm the patient has no contraindications to NIPS such as known vanishing twin or active maternal malignancy 1, 3

Partner Testing Requirement

If the patient tests positive as a carrier for any autosomal recessive condition, partner testing must be offered and should be covered to determine couple-based risk 1. At least 94% of CF and SMA carriers' partners undergo testing in clinical practice, identifying at-risk couples at a rate of approximately 1 in 240 4.