Non-invasive Prenatal Testing Using Cell-free Fetal DNA (cffDNA)
Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018
Circulating cell-free fetal DNA (cffDNA) crosses the placenta and can be isolated in maternal plasma. As early as 8-10 weeks of gestation these fetal DNA fragments can comprise 6-10% of the total cell free DNA in maternal plasma. Laboratories have developed tests that analyze cffDNA as a non-invasive screening tool for detecting fetal chromosomal abnormalities such as trisomy 21 (Down Syndrome), trisomy 18 (Edward Syndrome), and trisomy 13 (Patau Syndrome). Examples of commercially available test kits include, but are not limited to:
Tradename of Kit
Can be done at or after
|VisibiliT™||21, 18, and gender||10 weeks gestation|
|MaterniT21™ PLUS||21, 18, and 13 & sex aneuploidies||10 weeks gestation|
|Harmony™||21, 18, and 13||10 weeks gestation|
|Panorama™||21, 18, and 13, & sex aneuploidies||9 weeks gestation|
|Verifi®||21, 18, and 13||10 weeks gestation|
|InformaSeq®||21, 18, and 13||10 weeks gestation|
|QNatal™ Advanced||21, 18, and 13||10 weeks gestation|
Some of these tests have also been investigated for the use in detecting sex-linked abnormalities such as Turner Syndrome (XO in females) and Klinefelter Syndrome (XXX or XXY in males). Laboratories have also explored the potential for identifying fetal Rh status using the cell-free fetal DNA technology (e.g., SensiGene®, SEQureDX®).
Non-invasive prenatal testing of maternal plasma using cell-free fetal DNA (cffDNA) to detect fetal aneuploidy is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Non-invasive prenatal testing of maternal plasma using cell-free fetal DNA (cffDNA) when karyotyping, aneuploidy FISH, and/or array-comparative genomic hybridization have already been performed during the current pregnancy is not medically necessary.
Non-invasive prenatal testing of maternal plasma using cell-free fetal DNA (cffDNA) for the detection of other conditions including but not limited to the following is considered investigational:
Fetal sex chromosome aneuploidies (e.g., Turner Syndrome, Klinefelter Syndrome)
To determine fetal RHD genotyping
Non-invasive prenatal testing of maternal plasma using cell-free fetal DNA (cffDNA) is considered medically appropriate if ALL of the following criteria are met:
One (1) test per pregnancy, even if the first test was inconclusive
Test is done no sooner than 10 weeks gestation
Testing is indicated to determine presence of ANY ONE of the following chromosomal abnormalities:
Trisomy 21 - Down Syndrome
Trisomy 18 - Edward Syndrome
Trisomy 13 - Patau Syndrome
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits, or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
Before testing, women should receive counseling regarding the potential for false positive results. Studies to date do report rare false positives and no biological or processing explanations for these false positives have been discerned. In the absence of substantial data to characterize a false positive the professional organizations advise karyotyping tests (i.e. amniocentesis or chorionic villa sampling) to confirm a positive result.
There is insufficient evidence that noninvasive prenatal testing using cell-free fetal DNA is accurate for detecting fetal aneuploidy in twin and multiple pregnancies. The clinical utility of early sex chromosome aneuploidy detection is also unclear.
American College of Obstetricians and Gynecologists, Committee on Genetics; Society of Maternal-Fetal Medicine. (2015, September). Cell-free DNA Screening for fetal aneuploidy. Committee opinion number 640. Retrieved August 7, 2015 from http://www.acog.org.
American College of Obstetricians and Gynecologists, Committee on Genetics; Society of Maternal-Fetal Medicine. (2016, May). Practice bulletin number 163: Screening for fetal aneuploidy. Retrieved May 13, 2016 from http://www.acog.org.
Bianchi, D., Parker, L., Wentworth, J., Madankumar, R., Saffer, C., Das, A., et al. (2014). DNA sequencing versus standard prenatal aneuploidy screening. The New England Journal of Medicine. Vol. 370, (9), 800-808. (Level 2 evidence)
BlueCross BlueShield Association. Evidence Positioning System (5:2018). Noninvasive fetal RhD genotyping using cell-free fetal DNA. (2.04.108). Retrieved February 11, 2019 from https://www.evidencepositioningsystem.com/. (10 articles and/or guidelines reviewed)
BlueCross BlueShield Association. Evidence Positioning System. (8:2018). Noninvasive prenatal screening for fetal aneuploidies using cell-free fetal DNA. (4.01.21). Retrieved February 11, 2019 from https://www.evidencepositioningsystem.com/. (13 articles and/or guidelines reviewed)
Dondorp, W., de Wert, G., Bombard, Y., Bianchi, D., Bergmann, C., Borry, P., et al., (2015). Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening. European Journal of Human Genetics, 23, 1438-1450. (Level 5 evidence)
eviCore healthcare. (2019, January). Non-invasive prenatal testing guidelines. Retrieved February 11, 2019 from www.evicore.com. (11 articles and/or guidelines reviewed)
Gil, M., Accurti, V., Santa Cruz, B., Plana, M., and Nicholaides, K. (2017). Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis. Ultrasound Obstetrical Gynecology, 50, 302-314. (Level 2 evidence)
Li, W., Wang, P., Chuang, C., Chang, Y., Yang, M., Chen, C. et al. (2015). Noninvasive prenatal testing for fetal trisomy in a mixed risk factors pregnancy population. Taiwanese Journal of Obstetrics & Gynecology, 54,122-125. (Level 4 evidence)
Norton, M., Jocobsson, B., Swamy, G., Laurent, L., Ranzini, A., Brar, H., et al. (2015). Cell-free DNA analysis for noninvasive examination of trisomy. The New England Journal of Medicine. Vol. 372 (17), 1589-1597. (Level 2 evidence)
Taylor-Phillips, S., Freeman, K., Geppert, J., Agbebiyi, A., Uthman, O., Madan, J., et al. (2015). Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis. British Medical Journal (BMJ) 6:e010002. (Level 1 evidence)
ORIGINAL EFFECTIVE DATE: 6/8/2013
MOST RECENT REVIEW DATE: 3/28/2019
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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