Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Noninvasive Prenatal Screening for Fetal Aneuploidies Using Cell-Free Fetal DNA (Independence Administrators)

Policy #:06.02.47b

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract. The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

Nucleic acid sequencing-based testing of maternal plasma as a screen for fetal aneuploidy (Trisomies 21, 13, 18) is considered medically necessary and, therefore, covered in women with singleton pregnancies undergoing screening for fetal aneuploidy.

EXPERIMENTAL/INVESTIGATIONAL

Nucleic acid sequencing-based testing of maternal plasma for fetal aneuploidy is considered experimental/investigational and, therefore, not covered in women with twin or multiple gestation pregnancies because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.

Nucleic acid sequencing-based testing of maternal plasma for fetal sex chromosome aneuploidies is considered experimental/investigational and, therefore, not covered in because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.

Nucleic acid sequencing-based testing of maternal plasma for microdeletions is considered experimental/investigational and, therefore, not covered in because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.
Guidelines

Studies published to date report rare but occasional false positives. In these studies, the actual false positive test results were not always borderline; some were clearly above the assay cutoff value, and no processing or biological explanations for the false-positive results were reported.

According to ACOG:
  • Karyotyping should be performed for confirmation of abnormal results to exclude the possibility of a false positive nucleic acid sequencing–based test.
  • Before testing, women should be counseled about the risk of a false positive test.

In some cases, tissue samples from CVS or amniocentesis may be insufficient for karyotyping; confirmation by specific fluorescent in situ hybridization (FISH) assay is acceptable for these samples.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, Noninvasive Prenatal Testing for Fetal Aneuploidies Using Cell-Free Fetal DNA services covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

However, Noninvasive Prenatal Testing for Fetal Aneuploidies Using Cell-Free Fetal DNA services that are identified in this policy as experimental/investigational are not eligible for coverage or reimbursement by the Company.

The Company’s laboratory network has extensive genetic testing capabilities; therefore, providers should refer members only to participating laboratories for covered services. In the unusual circumstance that a specific covered test and related services are not available through a participating laboratory, providers must contact the Company to obtain preapproval.

Members who have out-of-network benefits may choose to use a non-participating laboratory for a medically necessary service, but they will have greater out-of-pocket costs associated with that service. In addition, the member will be financially responsible for the entire cost of any service that is non-covered (e.g., a service that is considered experimental/investigational).

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

None of the commercially available sequencing assays for detection ofT21, T18, and T13 or other chromosomal abnormalities has been submitted to or reviewed by the U.S. Food and Drug Administration (FDA). Clinical laboratories may develop and validate tests in-house (laboratory-developed tests [LDTs]; previously called “home-brew”) and market them as a laboratory service; LDTs must meet the general regulatory standards of the Clinical Laboratory Improvement Act (CLIA). Laboratories offering LDTs must be licensed by CLIA for high-complexity testing. Information on commercially available tests is as follows:
  • In October 2011, Sequenom (San Diego, CA) introduced its MaterniT21™ test to test for trisomy 21, 18 and 13. The test is offered through the company’s CLIA laboratory, the Sequenom Center for Molecular Medicine. (Uses MPS; reports results as positive or negative.) As of October 2014, Sequenom is offering the MaterniT21 PLUS test™ which tests for trisomy 21, 18 and 13 and also reports fetal sex aneuploidies, trisomies 16 and 22, and selected microdeletions as additional findings.
  • In March 2012, Illumina (Redwood, CA; formerly Verinata Health) launched its Verifi® prenatal test for trisomy 21, 18, and 13. (Uses MPS and calculates a normalized chromosomal value [NPS]; reports results as 1 of 3 categories: No Aneuploidy Detected, Aneuploidy Detected, or Aneuploidy Suspected.)
  • In May 2012, Ariosa Diagnostics (San Jose, CA; formerly Aria) launched its Harmony™ test for trisomy 21 and 18. (Uses directed DNA analysis, results reported as risk score.)
  • In March 2013, Natera (San Carlos, CA) introduced its Panorama™ prenatal test for detecting trisomy 21, 18 and 13, as well as for detecting select sex chromosome abnormalities. The test is available at ARUP Laboratories. (Uses SNP technology; results reported as risk score.)

BILLING GUIDELINES

Procedure code 81420 is not specific to the depth of sequencing; therefore, it would include deeper sequencing such as for microdeletion syndromes. Therefore, it would be incorrect to additionally report procedure code 88271: Molecular cytogenetics; DNA probe, each (e.g., FISH) in addition to procedure code 81420 for microdeletion testing.

Description

Fetal chromosomal abnormalities occur in approximately 1 in 160 live births. Most fetal chromosomal abnormalities are aneuploidies, defined as an abnormal number of chromosomes. The trisomy syndromes are aneuploidies involving 3 copies of 1 chromosome. The most important risk factor for trisomy syndromes is maternal age, with an approximate risk of 1 in 1500 in young women that increases to nearly 1 in 10 by age 48.

T21 (Down syndrome) is the most common cause of human birth defects and provides the impetus for current maternal serum screening programs. Other trisomy syndromes include T18 (Edwards syndrome), and T13 (Patau syndrome), which are the next most common forms of fetal aneuploidy in fetuses that survive to birth. The prevalence of these other aneuploidies is much lower than the prevalence of T21, and identifying them is not currently the main intent of prenatal screening programs. Also, the clinical implications of identifying trisomy 18 and 13 are unclear, as most fetuses with trisomy 18 and 13 do not survive to term.

Sex chromosome aneuploidies (e.g., 45,X [Turner syndrome]; 47,XXY, 47,XYY) occur in approximately 1 in 400 live births. These aneuploidies are typically diagnosed postnatally, sometimes not until adulthood, such as during an evaluation of diminished fertility. Alternatively, sex chromosome aneuploidies may be diagnosed incidentally during invasive karyotype testing of pregnant women at high risk for Down syndrome. The net clinical value of prenatal diagnosis of sex chromosome aneuploidies is unclear.

Potential benefits of early identification such as the opportunity for early management of the manifestations of the condition, must be balanced against potential harms that can include stigmatization and distortion of a family’s view of the child.

Current national guidelines recommend that all pregnant women be offered screening for fetal aneuploidy (referring specifically to T21, T18, and T13) before 20 weeks of gestation, regardless of age. Combinations of maternal serum markers and fetal ultrasound done at various stages of pregnancy are used, but there is not a standardized approach. The detection rate for various combinations of noninvasive testing ranges from 60% to 96% when the false-positive rate is set at 5%. When tests indicate a high risk of a trisomy syndrome, direct karyotyping of fetal tissue obtained by amniocentesis or chorionic villous sampling (CVS) is required to confirm that T21 or another trisomy is present. Both amniocentesis and CVS are invasive procedures and have an associated risk of miscarriage. A new screening strategy that reduces unnecessary amniocentesis and CVS procedures and increases detection of T 21, T18, and T13 has the potential to improve outcomes.

Commercial, noninvasive, sequencing-based testing of maternal serum for fetal trisomy syndromes has recently become available and has the potential to substantially alter the current approach to screening. The test technology involves detection of fetal cell-free DNA fragments present in the plasma of pregnant women. As early as 8 to 10 weeks of gestation, these fetal DNA fragments comprise 6% to 10% or more of the total cell-free DNA in a maternal plasma sample. The tests are unable to provide a result if fetal fraction is too low, that is, below about 4%. Fetal fraction can be affected by maternal and fetal characteristics. For example, fetal fraction was found to be lower at higher maternal weights and higher with increasing fetal crown-rump length.

Sequencing-based tests use 1 of 2 general approaches to analyzing cell-free DNA. The first category of tests uses quantitative or counting methods. The most widely used technique to date uses massively parallel sequencing (MPS; also known as next-generation or “next gen” sequencing). DNA fragments are amplified by polymerase chain reaction; during the sequencing process, the amplified fragments are spatially segregated and sequenced simultaneously in a massively parallel fashion. Sequenced fragments can be mapped to the reference human genome in order to obtain numbers of fragment counts per chromosome. The sequencing-derived percent of fragments from the chromosome of interest reflects the chromosomal representation of the maternal and fetal DNA fragments in the original maternal plasma sample. Another technique is direct DNA analysis, which analyzes specific cell-free DNA fragments across samples and requires approximately a tenth the number of cell-free DNA fragments as MPS. The digital analysis of selected regions (DANSR™) is an assay that uses direct DNA analysis.

The second general approach is single nucleotide polymorphism (SNP)--based methods. These use targeted amplification and analysis of approximately 20,000 SNPs on selected chromosomes (e.g., 21, 18, 13) in a single reaction. A statistical algorithm is used to determine the number of each type of chromosome.

Noninvasive prenatal testing analyzing cell-free fetal DNA in maternal serum is a potential complement or alternative to conventional serum screening.

To be clinically useful, the technology must be sensitive enough to detect a slight shift in DNA fragment counts among the small fetal fragment representation of a genome with a trisomic chromosome against a large euploid maternal background. Whether sequencing-based assays require confirmation by invasive procedures and karyotyping depends on assay performance. However, discrepancies between sequencing and invasive test results that may occur for biological reasons could make confirmation by invasive testing necessary at least in some cases, regardless of sequencing test performance characteristics.

Assessment of a diagnostic technology such as maternal plasma DNA sequencing tests typically focuses on 3 parameters: (1) analytic validity; (2) clinical validity (i.e., sensitivity and specificity) in appropriate populations of individuals; and (3) demonstration that the diagnostic information can be used to improve individual health outcomes (clinical utility).

ANALYTIC VALIDITY

Although all currently available commercially available tests use MPS, actual performance and interpretive procedures vary considerably. Clinical sequencing in general is not standardized or regulated by FDA or other regulatory agencies, and neither the routine quality control procedures used for each of these tests, nor the analytic performance metrics have been published.

CLINICAL VALIDITY

Data from the available published studies consistently reported a very high sensitivity and specificity of maternal plasma DNA sequencing-based tests for detecting T21 in high-risk women with singleton pregnancies. There are fewer data on the diagnostic performance of sequencing-based tests for detecting T13, T18 and sex chromosome aneuploidies. The available data suggest that diagnostic performance for detecting these other fetal aneuploidies is not as high as it is for detection of T21.

The available prospective studies in general population samples (which include both high- and average-risk women), including the large Norton et al 2015 study, have found high sensitivity and specificity rates, similar to that seen in high-risk women. In the Norton study, although PPV was lower in the subsample of low-risk women than in the general population PPV of cell-free DNA testing was much higher than standard screening.

For women with multiple gestation pregnancies, there is insufficient evidence to draw conclusions about the diagnostic accuracy of sequencing-based tests for detecting fetal aneuploidies.

CLINICAL UTILITY

There is no published direct evidence that managing individuals using sequencing-based testing improves health outcomes compared with standard screening. Modeling studies using published estimates of diagnostic accuracy and other parameters predict that sequencing-based testing as an alternative to standard screening will lead to an increase in the number of T21 cases detected and, when included in the model, a large decrease in the number of invasive tests and associated miscarriages. The number of T18 and T13 cases detected is similar or higher with sequencing-based testing, although this is more difficult to estimate because of the lower prevalence of these aneuploidies, especially with T13. The impact of screening for sex chromosome aneuploidies has not been modeled in published studies.

The evidence for noninvasive prenatal screening (NIPS) using cell-free DNA to detect microdeletions in individuals with singleton, twin, or multiple pregnancies includes several studies on analytical and clinical validity. Relevant outcomes are test accuracy and validity, other test performance measures, morbid events, resource utilization, and treatment-related morbidity. The available studies on clinical validity have limitations (e.g., missing data on confirmatory testing, false-negatives) and the added benefit of NIPS compared with current approaches is unclear. Moreover, the clinical utility of NIPS for microdeletions remains unclear and has not been evaluated in published studies. The evidence is insufficient to determine the effects of the technology on health outcomes.

AMERICAN COLLEGE OF MEDICAL GENETICS AND GENOMICS

In 2013, the American College of Medical Genetics and Genomics (ACMG) published a statement on noninvasive prenatal screening for fetal aneuploidy that addresses challenges in incorporating noninvasive testing into clinical practice. Limitations identified by the organization include that chromosomal abnormalities such as unbalanced translocations, deletions and duplications, single-gene mutations and neural tube defects cannot be detected by the new tests. Moreover, it currently takes longer to obtain test results than with maternal serum analytes. ACMG also stated that pretest and post-test counseling should be performed by trained personnel.

AMERICAN COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTS AND SOCIETY FOR MATERNAL-FETAL MEDICINE

In November 2012, the American College of Obstetricians and Gynecologists (ACOG) released a committee opinion on noninvasive testing for fetal aneuploidy The Committee Opinion was issued jointly with the Society for Maternal-Fetal Medicine Publications Committee. ACOG recommended that maternal plasma DNA testing be offered to individuals at increased risk of fetal aneuploidy. They did not recommend that the test be offered to women who are not at high risk or to women with multiple gestations. ACOG further recommended that women be counseled before testing about the limitations of the test and recommended confirmation of positive findings with CVS or amniocentesis. The document noted that the content reflected emerging clinical and scientific advances and is subject to change as additional information becomes available. The Committee Opinion did not include an explicit review of the literature.

In a 2015 committee opinion, the American College of Obstetricians and Gynecologists (ACOG) recommends that all patients receive information on the risks and benefits of various methods of prenatal screening and diagnostic testing, including the option of no testing. False-positive findings have been found to be associated with factors including placental mosaicism, vanishing twins and maternal malignancies. In its 2015 committee opinion, ACOG recommended diagnostic testing to confirm positive cell-free DNA tests, and that management decisions not be based solely on the results of cell-free DNA testing. ACOG further recommends that patients with indeterminate or uninterpretable (i.e., “no call”) cell-free DNA test results be referred for genetic counseling and offered ultrasound evaluation and diagnostic testing because “no call” findings have been associated with an increased risk of aneuploidy.

In sum, published studies on all commercially available tests, and meta-analyses of these studies, have consistently demonstrated very high sensitivity and specificity for detecting Down syndrome (trisomy 21 [T21]) in singleton pregnancies. Most of the studies included only women at high risk of T21. For average risk women, available studies suggest test performance similar to that reported in high-risk women.

Direct evidence of clinical utility is not available. A 2013 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessment modeled comparative outcomes based on the published data on test performance, published estimates of standard screening performance, individual uptake of confirmatory testing, and miscarriage rates associated with invasive procedures. For each comparison and in each risk population, sequencing-based testing improved outcomes, i.e., increased the rate of Down syndrome detection and reduced the number of invasive procedures and procedure-related miscarriages. In the modeling, the negative predictive value of testing approached 100% across the range of aneuploidy risk, while the positive predictive value varied widely according to baseline risk. The variable positive predictive value highlights the possibility of a false positive finding and thus testing using karyotyping is necessary to confirm a positive result.

There is less published evidence on the diagnostic performance of sequencing-based tests for detecting T18, T13 and sex chromosome anomalies, and most of the available studies were conducted in high-risk pregnancies. Meta-analyses of available data suggest high sensitivities and specificities, but the small number of cases, especially for T13, makes definitive conclusions difficult. The findings of a decision analysis study included in the 2014 BCBSA TEC Assessment suggest similar rates of T13 and T18 detection to standard noninvasive screening; the analysis assumed that T13 and T18 screening would be done in conjunction with T21 screening. Due to the low survival rate, the clinical benefit of identifying trisomy 18 and 13 are unclear. The clinical utility of early sex chromosome aneuploidy detection is also unclear.

As noted in the 2015 ACOG committee opinion, cell-free DNA screening does not assess risk of anomalies such as neural tube defects. Patients should continue to be offered ultrasound or maternal serum alpha-fetoprotein screening, regardless of the type of serum screening selected. This opinion also states that routine cell-free DNA screening for microdeletion syndromes should not be performed. Furthermore, this opinion communicates that given the performance of conventional screening methods, the limitations of cell-free DNA screening performance, and the limited data on cost-effectiveness in the low-risk obstetric population, conventional screening methods remain the most appropriate choice for first-line screening for most women in the general obstetric population.
References


American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstet Gynecol. Jan 2007;109(1):217-227. PMID 17197615

American College of Obstetricians and Gynecologists (ACOG). Committee Opinion: Noninvasive Prenatal Testing for Fetal Aneuploidy. 2012;
http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Genetics/Noninvasive_Prenatal_Testing_for_Fetal_Aneuploidy. Accessed December, 2014

Ashoor G, Syngelaki A, Wagner M, et al. Chromosome-selective sequencing of maternal plasma cell-free DNA for first-trimester detection of trisomy 21 and trisomy 18. Am J Obstet Gynecol. Apr 2012;206(4):322 e321-325. PMID 22464073

Ashoor G, Syngelaki A, Poon LC, et al. Fetal fraction in maternal plasma cell-free DNA at 11-13 weeks' gestation: relation to maternal and fetal characteristics. Ultrasound Obstet Gynecol. Jan 2013;41(1):26-32. PMID 23108725

Benn P, Borell A, Chiu R, et al. Position statement from the Aneuploidy Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis. Prenat Diagn. Jul 2013;33(7):622-629. PMID 23616385

Bianchi DW, Platt LD, Goldberg JD, et al. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol. May 2012;119(5):890-901. PMID 22362253

Bianchi DW, Parker RL, Wentworth J, et al. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med. Feb 27 2014;370(9):799-808. PMID 24571752

Blue Cross Blue Shield Association Technology Evaluation Center (TEC). Sequencing-based tests to determine fetal down syndrome (trisomy 21) from maternal plasma DNA. TEC Assessments 2013; Volume 27, Tab 10. PMID

Blue Cross Blue Shield Association Technology Evaluation Center (TEC). Noninvasive maternal plasma sequencing-based screening for fetal aneuploidies other than trisomy 21. TEC Assessments 2014; Volume 28, Tab TBD. PMID

Canick JA, Kloza EM, Lambert-Messerlian GM, et al. DNA sequencing of maternal plasma to identify Down syndrome and other trisomies in multiple gestations. Prenat Diagn. May 14 2012:1-5. PMID 22585317

Committee Opinion No. 640: Cell-free DNA Screening for Fetal Aneuploidy. Obstet Gynecol. Jun 25 2015. PMID 26114726

Devers PL, Cronister A, Ormond KE, et al. Noninvasive prenatal testing/noninvasive prenatal diagnosis: the position of the National Society of Genetic Counselors. J Genet Couns. Jun 2013;22(3):291-295. PMID 23334531

Ehrich M, Deciu C, Zwiefelhofer T, et al. Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am J Obstet Gynecol. Mar 2011;204(3):205 e201-211. PMID 21310373

Garfield SS, Armstrong SO. Clinical and cost consequences of incorporating a novel non-invasive prenatal test into the diagnostic pathway for fetal trisomies. J Managed Care Med. 2012;15(2):34-41. PMID

Gil MM, Quezada MS, Bregant B, et al. Implementation of maternal blood cell-free DNA testing in early screening for aneuploidies. Ultrasound Obstet Gynecol. Jul 2013;42(1):34-40. PMID 23744609

Gil MM, Akolekar R, Quezada MS, et al. Analysis of Cell-Free DNA in Maternal Blood in Screening for Aneuploidies: Meta-Analysis. Fetal Diagn Ther. Feb 8 2014. PMID 24513694

Gregg AR, Gross SJ, Best RG, et al. ACMG statement on noninvasive prenatal screening for fetal aneuploidy. Genet Med. May 2013;15(5):395-398. PMID 23558255

Nicolaides KH, Syngelaki A, Ashoor G, et al. Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population. Am J Obstet Gynecol. 2012;207. PMID

Nicolaides KH, Syngelaki A, Gil M, et al. Validation of targeted sequencing of single-nucleotide polymorphisms for non-invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X, and Y. Prenat Diagn. Jun 2013;33(6):575-579. PMID 23613152

Norton ME, Brar H, Weiss J, et al. Non-Invasive Chromosomal Evaluation (NICE) Study: Results of aMulticenter, Prospective, Cohort Study for Detection of Fetal Trisomy 21 and Trisomy 18. Am J Obstet Gynecol. 2012.

Norton ME, Jacobsson B, Swamy GK, et al. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med. Apr 23 2015;372(17):1589-1597. PMID 25830321

Ohno M, Caughey A. The role of noninvasive prenatal testing as a diagnostic versus a screening tool--a costeffectiveness analysis. Prenat Diagn. Jul 2013;33(7):630-635. PMID 23674316

Palomaki GE, Kloza EM, Lambert-Messerlian GM, et al. DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med. Nov 2011;13(11):913-920. PMID 22005709

Palomaki GE, Deciu C, Kloza EM, et al. DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study. Genet Med. Mar 2012;14(3):296-305. PMID 22281937

Porreco RP, Garite TJ, Maurel K, et al. Noninvasive prenatal screening for fetal trisomies 21, 18, 13 and the common sex chromosome aneuploidies from maternal blood using massively parallel genomic sequencing of DNA. Am J Obstet Gynecol. Mar 19 2014. PMID 24657131

Quezada MS, Del Mar Gil M, Francisco C, et al. Screening for trisomies 21, 18 and 13 cell-free DNA analysis of maternal blood at 10-11 weeks' gestation and the combined test at 11-13 weeks. Ultrasound Obstet Gynecol. Sep 24 2014. PMID 25251385

Sehnert AJ, Rhees B, Comstock D, et al. Optimal detection of fetal chromosomal abnormalities by massively parallel DNA sequencing of cell-free fetal DNA from maternal blood. Clin Chem. Jul 2011;57(7):1042-1049. PMID 21519036

Sparks AB, Struble CA, Wang ET, et al. Noninvasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18. Am J Obstet Gynecol. Apr 2012;206(4):319 e311-319. PMID 22464072

Sponsored by Aria Diagnostics Inc. Non-invasive Chromosomal Examination of Trisomy Study (NEXT) (NCT01511458). www.clinicaltrials.gov. Accessed December, 2014.

Sponsored by Centre Hospitalier Universitaire de Québec. Study of the Efficacy of New Non-invasive Prenatal Tests for Screening for Fetal Trisomies Using Maternal Blood (PEGASUS) (NCT01925742). www.clinicaltrials.gov. Accessed December, 2014.

Sponsored by Natera Inc. Prenatal Non-invasive Aneuploidy Test Utilizing SNPs Trial (PreNATUS) (NCT01545674). www.clinicaltrials.gov. Accessed December, 2014.

Sponsored by Sequenom Inc. Clinical Evaluation of the SEQureDx T21 Test in Low Risk Pregnancies (NCT01597063). www.clinicaltrials.gov. Accessed December, 2014.

U.S. Food and Drug Adminstration (FDA). Ultra High Throughput Sequencing for Clinical Diagnostic Applications - Approaches to Assess Analytical Validity, June 23, 2011 (Archived Content). http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/ucm255327.htm. Accessed December, 2014.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

MEDICALLY NECESSARY

0009M, 81420, 81507

THE FOLLOWING CODE IS APPROPRIATE WHEN REPORTED BY A GENETIC COUNSELOR. WHEN PERFORMED BY A PHYSICIAN OR OTHER QUALIFIED HEALTH CARE PROFESSIONAL, THE PHYSICIAN OR OTHER QUALIFIED HEALTH CARE PROFESSIONAL SHOULD USE THE APPROPRIATE EVALUATION AND MANAGEMENT EXAM CODES:
96040

EXPERIMENTAL/INVESTIGATIONAL
81422



Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

N/A


HCPCS Level II Code Number(s)



THE FOLLOWING CODE IS USED TO REPRESENT INTERPRETATION AND REPORT:

G0452 Molecular pathology procedure; physician interpretation and report

THE FOLLOWING CODE IS APPROPRIATE WHEN REPORTED BY A GENETIC COUNSELOR. WHEN PERFORMED BY A PHYSICIAN OR OTHER QUALIFIED HEALTH CARE PROFESSIONAL, THE PHYSICIAN OR OTHER QUALIFIED HEALTH CARE PROFESSIONAL SHOULD USE THE APPROPRIATE EVALUATION AND MANAGEMENT EXAM CODES:

S0265 Genetic counseling, under physician supervision, each 15 minutes



Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References


Policy History

Revisions for 06.02.47b
05/08/2019This policy has been reissued in accordance with the Company's annual review process.
11/21/2018This policy has been reissued in accordance with the Company's annual review process.


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 01/01/2017
Version Issued Date: 12/30/2016
Version Reissued Date: 05/08/2019

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