Sunflower Health Plan Concert Genetic Testing: Non invasive Prenatal Screening (PDF) Form

Concert Genetic Testing: Non-invasive Prenatal Screening (NIPS) V2.2023 Date of Last Revision: 3/1/2023 CONCERT GENETIC TESTING: NON- INVASIVE PRENATAL SCREENING (NIPS) Other common names for this test include: Non-invasive Prenatal Testing (NIPT), Non-invasive Prenatal Screening (NIPS), Cell-free DNA Testing (cfDNA), Cell-free Fetal DNA Testing See Important Reminder at the end of this policy for important regulatory and legal information. OVERVIEW Non-invasive prenatal screening (NIPS) is a sequencing test performed on placental cell-free DNA found in maternal serum and is most commonly used to screen for fetal aneuploidy (trisomy 21, trisomy 13, and trisomy 18); sex chromosomes are also screened for fetal sex determination and sex chromosome aneuploidy. NIPS is a screening test and does not provide definitive diagnosis for a fetus. When NIPS is positive, or high risk, for a genetic abnormality, the fetus is at increased risk for that condition. Further testing would be necessary to exclude the possibility of a false-positive. NIPS has recently expanded to include microdeletion and microduplication syndromes, as well as single-gene disorders, although this is an area of ongoing research. NIPS has also expanded to predict twin zygosity (i.e., monozygotic versus dizygotic twins). Monozygotic twins have a higher risk for certain complications, such as twin-twin transfusion syndrome (TTTS). POLICY REFERENCE TABLE Below are a list of higher volume tests and the associated laboratories for each coverage criteria section. This list is not all inclusive. Coding Implications 1 Concert Genetic Testing: Non-invasive Prenatal Screening (NIPS) V2.2023 Date of Last Revision: 3/1/2023 This clinical policy references Current Procedural Terminology (CPT®). CPT® is a registered trademark of the American Medical Association. All CPT codes and descriptions are copyrighted 2022, American Medical Association. All rights reserved. CPT codes and CPT descriptions are from the current manuals and those included herein are not intended to be all-inclusive and are included for informational purposes only. Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services. Coverage Criteria Coverage Criteria Sections Sections Non-invasive Non-invasive Prenatal Screening Prenatal Screening (NIPS) for (NIPS) for Chromosome 13, 18, Chromosome 13, 18, 21, X and Y 21, X and Y Aneuploidies Aneuploidies Non-invasive Non-invasive Prenatal Screening Prenatal Screening (NIPS) for (NIPS) for Microdeletions Microdeletions Non-invasive Non-invasive Prenatal Screening Prenatal Screening (NIPS) for Single- (NIPS) for Single- Gene Disorders Gene Disorders Maternal Serum Maternal Serum Screening (MSS) Screening (MSS) Example Tests (Labs) Example Tests (Labs) Common CPT Common CPT Codes Codes Common ICD Common ICD Codes Codes Ref Ref Vasistera (Natera) Vasistera (Natera) 0327U 0327U Panorama Prenatal Panel (Natera) Panorama Prenatal Panel (Natera) 81420, 0060U 81420, 0060U Singleton NIPS (chromosomes 13, 18, Singleton NIPS (chromosomes 13, 18, 21) (Invitae) 21) (Invitae) MaterniT21 PLUS (Integrated MaterniT21 PLUS (Integrated Genetics) Genetics) Harmony (BioReference Laboratories) 81507 Harmony (BioReference Laboratories) 81507 O09, O28, O30, O09, O28, O30, O35, Q90 O35, Q90 through Q99, through Q99, Z34, Z36.0 Z34, Z36.0 1, 2, 3, 1, 2, 3, 6 6 81420, 81422, 81420, 81422, 0060U 0060U Panorama - with microdeletion Panorama - with microdeletion syndromes (Natera) syndromes (Natera) MaterniT21 Plus Core + ESS MaterniT21 Plus Core + ESS (Integrated Genetics) (Integrated Genetics) Prequel Prenatal Screen + Prequel Prenatal Screen + Microdeletions (Myriad) Microdeletions (Myriad) Vistara (Single-Gene NIPT) (Natera) 81302, 81404, Vistara (Single-Gene NIPT) (Natera) 81302, 81404, 81406, 81407, 81406, 81407, 81408, 81442 81408, 81442 PreSeek Non-invasive Prenatal Gene PreSeek Non-invasive Prenatal Gene Sequencing Screen (Baylor Miraca Sequencing Screen (Baylor Miraca Genetics Laboratories) Genetics Laboratories) First Trimester Screen, HCG (Quest First Trimester Screen, HCG (Quest Diagnostics) Diagnostics) Quad Screen (Quest Diagnostics) Quad Screen (Quest Diagnostics) Serum Integrated Screen, Part 2 (Quest Serum Integrated Screen, Part 2 (Quest Diagnostics) Diagnostics) Penta Screen (Quest Diagnostics) Penta Screen (Quest Diagnostics) 81508 81508 81509, 81510, 81509, 81510, 81511, 81512 81511, 81512 81512 81512 O09, O28, O35, O09, O28, O35, Q90 through Q90 through Q99, Z34, Z36.0 Q99, Z34, Z36.0 3 3 4 4 5 5 O09, O28, O30, O09, O28, O30, O35, Q90 O35, Q90-Q99, Z34, Z36.0 through Q99, Z34, Z36.0 O09, O28, O30, O09, O28, O30, O35, Q90 O35, Q90 through Q99, through Q99, Z34, Z36.0 Z34, Z36.0 2 Concert Genetic Testing: Non-invasive Prenatal Screening (NIPS) V2.2023 Date of Last Revision: 3/1/2023 OTHER RELATED POLICIES This policy document provides coverage criteria for Non-Invasive Prenatal Screening (NIPS). Please refer to: ● Oncology: Circulating Tumor DNA and Circulating Tumor Cells (Liquid Biopsy) for criteria related to circulating tumor DNA (ctDNA) or circulating tumor cell testing performed on peripheral blood for cancer diagnosis, management and surveillance. ● Genetic Testing: Prenatal Diagnosis (via amniocentesis, CVS, or PUBS) and Pregnancy Loss for coverage related to prenatal and pregnancy loss diagnostic genetic testing. ● Genetic Testing: Prenatal and Preconception Carrier Screening for coverage criteria related to carrier screening for genetic disorders. ● Genetic Testing: Preimplantation Genetic Testing for coverage criteria related to genetic testing of embryos prior to in vitro fertilization. ● Genetic Testing: Multisystem Inherited Disorders, Intellectual Disability, and Developmental Delay for coverage criteria related to diagnostic genetic testing in the postnatal period. ● Genetic Testing: General Approach to Genetic Testing for coverage criteria related to non- invasive prenatal screening that is not specifically discussed in this or other non-general policies. CRITERIA It is the policy of health plans affiliated with Centene Corporation® that the specific genetic testing noted below is medically necessary when meeting the related criteria: 3 Concert Genetic Testing: Non-invasive Prenatal Screening (NIPS) V2.2023 Date of Last Revision: 3/1/2023 Non-invasive Prenatal Screening (NIPS) for Chromosome 13, 18, 21, X and Y Aneuploidies I. Noninvasive Prenatal Screening (NIPS) for trisomy 13, 18, 21, X and Y aneuploidy (81420, 81507, 0327U) may be considered medically necessary when: A. The member/enrollee has a singleton or twin pregnancy, AND B. The member/enrollee has received appropriate counseling about the benefits and limitations of this test by a prenatal care provider, a trained designee, or a genetic counselor. II. NIPS to predict twin zygosity (0060U) is considered investigational. III. NIPS for multiple gestation pregnancies (triplets or higher) is considered investigational. IV. NIPS is considered investigational for all other indications, including the following: A. For all other aneuploidies (other than trisomy 13, 18, and 21) B. NIPS performed simultaneously with maternal serum screening C. Use on a singleton pregnancy with a known vanishing twin D. For the sole purpose of fetal sex determination Non-invasive Prenatal Screening (NIPS) for Microdeletions I. NIPS for microdeletion and microduplications (81422, 0060U) is considered investigational. back to top back to top Non-invasive Prenatal Screening (NIPS) for Single-gene Disorders I. NIPS for mutations associated with single gene disorders (81302, 81404, 81406, 81407, 81408, 81442) is considered investigational. back to top 4 Concert Genetic Testing: Non-invasive Prenatal Screening (NIPS) V2.2023 Date of Last Revision: 3/1/2023 Maternal Serum Screening (MSS) I. Maternal serum screening for aneuploidy using no more than one of the following one time per pregnancy is considered medically necessary: A. First trimester screening (free or total beta-HCG and PAPP-A) (81508) B. Second trimester screening (hCG, msAFP, uE3, and DIA) (81509, 81510, 81511, 81512) C. Integrated, stepwise sequential, or contingent sequential screening (81508, 81509, 81510, 81511, 81512) D. Penta screen (hCG, msAFP, uE3, DIA, ITA) (81512) back to top NOTES AND DEFINITIONS Noninvasive prenatal screening (NIPS) is a screening test that is used to determine the risk of specific genetic disorders by analyzing traces of cell-free DNA (cfDNA) in a pregnant woman’s blood. Sequencing-based tests use 1 of 2 general approaches to analyze cell-free DNA. The most widely used technique to date uses massively parallel sequencing (MPS; also known as next- generation or “next gen” sequencing). The second general approach uses the single nucleotide polymorphism (SNP) method. Singleton pregnancy is a pregnancy with one fetus. Twin Zygosity testing is used to predict the degree of genetic similarity within each pair (i.e., monozygotic versus dizygotic). Monozygotic (genetically identical twins) are at a higher risk for pregnancy complications, such as twin-twin transfusion syndrome (TTTS). back to top 5 Concert Genetic Testing: Non-invasive Prenatal Screening (NIPS) V2.2023 Date of Last Revision: 3/1/2023 CLINICAL CONSIDERATIONS It is the policy of health plans affiliated with Centene Corporation® that the specific genetic testing noted below is medically necessary when meeting the related criteria: More than one cell-free DNA screen performed per pregnancy (defined by no more than one paid test per pregnancy) is not medically indicated. NIPS does not assess the risk of neural tube defects (NTDs). Guidelines recommend that patients should continue to be offered screening for NTDs via ultrasound or maternal serum alpha fetoprotein (msAFP). NIPS is a screening test and indicates an increased or decreased risk for the condition(s) being screened. NIPS is not diagnostic for any condition and pregnancy management decisions should not be based solely on the results of cell-free DNA screening. Karyotyping, FISH, or CMA would be necessary to exclude the possibility of a false-positive. Before testing, guidelines recommend that women be counseled about the risk of a false-positive result. False-positive findings have been associated with factors, including placental mosaicism, vanishing twin, maternal genetic condition, and maternal malignancy. ACOG Practice Guideline 226 (2020) recommends that all patients receive information on the risks and benefits of various methods of prenatal screening and diagnostic testing for fetal aneuploidies, including the option of no testing. ACOG also recommends that patients with indeterminate or uninterpretable (ie, "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. back to top BACKGROUND AND RATIONALE Non-invasive Prenatal Screening (NIPS) for Chromosome 13, 18, 21, X and Y Aneuploidy American College of Obstetricians and Gynecologists (ACOG) and Society for Maternal-Fetal Medicine (SMFM) ACOG and SMFM (2020) released a joint practice bulletin (No. 226) with the following recommendations for screening for fetal chromosomal abnormalities: 6 Concert Genetic Testing: Non-invasive Prenatal Screening (NIPS) V2.2023 Date of Last Revision: 3/1/2023 The following recommendations and conclusions are based on good and consistent scientific evidence (Level A): ● Cell-free DNA is the most sensitive and specific screening test for the common fetal aneuploidies. Nevertheless, it has the potential for false-positive and false-negative results. Furthermore, cell-free DNA testing is not equivalent to diagnostic testing. (p. e63) The following recommendations and conclusions are based on limited and inconsistent scientific evidence (Level B): ● Cell-free DNA screening can be performed in twin pregnancies. Overall, performance of screening for trisomy 21 by cell-free DNA in twin pregnancies is encouraging, but the total number of reported affected cases is small. Given the small number of affected cases it is difficult to determine an accurate detection rate for trisomy 18 and 13. (p. e64) Regarding prenatal screening for multiple gestation pregnancies of triplets or higher, Practice Bulletin No. 226 also states: “...there are no data available for serum screening for higher-order multiple gestations such as triplets and quadruplets.” (p. e59) Regarding screening a pregnancy with a vanishing twin: “In a patient with both a vanishing twin and a viable intrauterine pregnancy, cell-free DNA screening is not advised because of the high risk for aneuploidy in the nonviable sac or embryo, which can lead to false-positive results.” (p. e53) The Practice Bulletin No. 226 also notes that “[i]f screening is accepted, patients should have one prenatal screening approach, and should not have multiple screening tests performed simultaneously.” (p. e49) American College of Medical Genetics and Genomics (ACMG) ACMG (2016) published a position statement on noninvasive prenatal screening (NIPS) for fetal aneuploidy. ACMG recommends: ● Informing all pregnant women that NIPS is the most sensitive screening option for traditionally screened aneuploidies (i.e., T13, T18, and T21). (page 1059) ● Referring patients to a trained genetics professional when an increased risk of aneuploidy is reported after NIPS. (page 1059) 7 Concert Genetic Testing: Non-invasive Prenatal Screening (NIPS) V2.2023 Date of Last Revision: 3/1/2023 ● Providers should make efforts to deter patients from selecting sex chromosome aneuploidy screening for the sole purpose of biologic sex identification in the absence of a clinical indication for this information (p. 1060) Current ACMG practice guidelines (2022) “strongly recommends NIPS over traditional screening for all pregnant patients with singleton and twin gestations for fetal trisomies 21, 18, and 13 and strongly recommends NIPS be offered to patients to screen for fetal sex chromosome aneuploidy.” (p. 1 and p.5) National Society for Genetic Counselors (NSGC) The National Society for Genetic Counselors adopted the following statement updated in 2021 supporting prenatal cell-free DNA (cfDNA) screening as an option for pregnant patients: The National Society of Genetic Counselors believes that all pregnant patients, regardless of aneuploidy risk, should have access to prenatal aneuploidy screening using cell-free DNA (cfDNA)*. Healthcare providers should present cfDNA screening for aneuploidy within the context of other available prenatal screening and diagnostic testing options. Included in this discussion should be the option of pursuing diagnostic testing as a first line approach or declining all screening/testing. Pretest counseling should also include a discussion of the individual patient’s values, preferences, and needs, as well as the benefits and limitations of cfDNA screening. Many factors influence cfDNA screening performance; therefore, it may not be appropriate for every clinical scenario. Additionally, some laboratories offer screening for conditions beyond common aneuploidies, so it is essential to consider the test’s positive predictive value, particularly when the prevalence of the disorder is low. Patients who receive increased risk or inconclusive/atypical results should receive post- test genetic counseling with a knowledgeable healthcare provider, such as a genetic counselor. In such cases, confirmatory diagnostic testing may be indicated, and patients should be counseled that no irreversible actions should be taken based on the cfDNA screening alone. Non-invasive Prenatal Screening (NIPS) for Microdeletions American College of Obstetricians and Gynecologists (ACOG) and Society for Maternal-Fetal Medicine (SMFM) 8 Concert Genetic Testing: Non-invasive Prenatal Screening (NIPS) V2.2023 Date of Last Revision: 3/1/2023 ACOG and SMFM (2020) released a joint practice bulletin (No. 226) with the following recommendations for screening for fetal chromosomal abnormalities: Screening for a limited number of microdeletions with cell-free DNA is available; however, this testing has not been validated clinically and is not recommended. Although microdeletions are relatively common when considered in aggregate, cell-free DNA panels only include a few specific clinically significant microdeletions and these are very rare. Therefore, the PPV for these disorders is much lower than for common trisomies. (p. e53) Non-invasive Prenatal Screening (NIPS) for Single Gene Disorders The American College of Obstetricians and Gynecologists (ACOG) ACOG issued a practice advisory for the use of cell-free DNA to screen for single-gene disorders (February 2019, reaffirmed March 2020), which states the following: The continued innovation in cell-free technology combined with the desire for a maternal blood test to predict the risk for fetal genetic disorders during a pregnancy has broadened the application of cell-free DNA screening beyond aneuploidy to single-gene disorders. Examples of single-gene disorders include various skeletal dysplasias, sickle cell disease and cystic fibrosis. Although this technology is available clinically and marketed as a single-gene disorder prenatal screening option for obstetric care providers to consider in their practice, often in presence of advanced paternal age, there has not been sufficient data to provide information regarding accuracy and positive and negative predictive value in the general population. For this reason, single-gene cell-free DNA screening is not currently recommended in pregnancy. Maternal Serum Screening The American College of Obstetricians and Gynecologists ● All women should be offered the option of aneuploidy screening or diagnostic testing for fetal genetic disorders, regardless of maternal age. The choice of screening test is affected by many factors, including a desire for information before delivery, prior obstetric history, family history, and the number of fetuses. Other factors to be considered include gestational age at presentation, the availability of a reliable nuchal translucency 9 Concert Genetic Testing: Non-invasive Prenatal Screening (NIPS) V2.2023 Date of Last Revision: 3/1/2023 measurement, screening test sensitivity and limitations, the cost of screening, the constraints of long-term care of an affected child, and options for pregnancy care or termination for an abnormal diagnostic test result. No one test is superior for all test characteristics and not every test is available at all centers. Each test has advantages and disadvantages that should be discussed with each patient, with the appropriate test offered based on her concerns, needs, and values. (ACOG 163, pg 6) ● Stepwise and Contingent screening was developed to maintain a high detection rate using the combined first- and second- trimester screening approach while also reporting the patient’s first-trimester screening test risk, which allows for earlier management options. Using stepwise sequential screening, the patient is given a preliminary risk estimate after completion of the first-trimester analytes and nuchal translucency screening. If the first- trimester screening result indicates that the risk of aneuploidy is greater than the laboratory-derived positive screening cutoff, the patient is notified and offered a diagnostic test or cell-free DNA screening, and the screening protocol is discontinued. If the patient has a lower risk than the cut off level, they are informed that they have received a negative screening test result and proceeds to quad screening in the second trimester. Sequential screening has a detection rate of 91 to 93% with a positive screening test result rate of 4 to 5%. (ACOG 163, p. 5) ● In locations where a nuchal translucency measurement by a certified ultrasonographer is unavailable, or if fetal position, maternal body habitus, or imaging properties preclude an accurate nuchal translucency measurement, serum integrated screening can be offered. (ACOG 163, p 5) Reviews, Revisions, and Approvals Policy developed REFERENCES back to top Revision Date 03/23 Approval Date 03/23 1. Gregg AR, Skotko BG, Benkendorf JL, et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016;18(10):1056-1065. doi:10.1038/gim.2016.97 2. “Prenatal Cell-Free DNA Screening.” Position Statement from National Society of Genetic Counselors. https://www.nsgc.org/Policy-Research-and-Publications/Position- 10 Concert Genetic Testing: Non-invasive Prenatal Screening (NIPS) V2.2023 Date of Last Revision: 3/1/2023 Statements/Position-Statements/Post/prenatal-cell-free-dna-screening-1. Released October 11, 2016. Revised April 2021. 3. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics; Committee on Genetics; Society for Maternal-Fetal Medicine. Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin, Number 226. Obstet Gynecol. 2020;136(4):e48-e69. doi:10.1097/AOG.0000000000004084 4. “Cell-free DNA to Screen for Single-Gene Disorders”. Practice Advisory from The American College of Obstetricians and Gynecologists. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2019/02/cell- free-dna-to-screen-for-single-gene-disorders Published February 2019. Reaffirmed March 2020. 5. Practice Bulletin No. 163: Screening for Fetal Aneuploidy. Obstet Gynecol. 2016;127(5):e123-e137. doi:10.1097/AOG.0000000000001406 6. Dungan JS, Klugman S, Darilek S, et al. Noninvasive prenatal screening (NIPS) for fetal chromosome abnormalities in a general-risk population: An evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2022 Dec 13:S1098-3600(22)01004-8. doi: 10.1016/j.gim.2022.11.004. Epub ahead of print. PMID: 36524989. back to top Important Reminder This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable. The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, 11 Concert Genetic Testing: Non-invasive Prenatal Screening (NIPS) V2.2023 Date of Last Revision: 3/1/2023 contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures. This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time. This clinical policy does not constitute medical advice, medical treatment or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members/enrollees. This clinical policy is not intended to recommend treatment for members/enrollees. Members/enrollees should consult with their treating physician in connection with diagnosis and treatment decisions. Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan. This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members/enrollees and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members/enrollees and their representatives agree to be bound by such terms and conditions by providing services to members/enrollees and/or submitting claims for payment for such services. Note: For Medicaid members/enrollees, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy. Note: For Medicare members/enrollees, to ensure consistency with the Medicare National Coverage Determinations (NCD) and Local Coverage Determinations (LCD), all applicable NCDs, LCDs, and Medicare Coverage Articles should be reviewed prior to applying the criteria set forth in this clinical policy. Refer to the CMS website at http://www.cms.gov for additional information. 12 Concert Genetic Testing: Non-invasive Prenatal Screening (NIPS) V2.2023 Date of Last Revision: 3/1/2023 ©2023 Centene Corporation. All rights reserved. All materials are exclusively owned by Centene Corporation and are protected by United States copyright law and international copyright law. No part of this publication may be reproduced, copied, modified, distributed, displayed, stored in a retrieval system, transmitted in any form or by any means, or otherwise published without the prior written permission of Centene Corporation. You may not alter or remove any trademark, copyright or other notice contained herein. Centene® and Centene Corporation® are registered trademarks exclusively owned by Centene Corporation. 13