BlueCross BlueShield of Tennessee Medical Policy Manual

Non-invasive Prenatal Testing Using Cell-free Fetal DNA (cffDNA)

Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018

DESCRIPTION

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

Trisomy Tested

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®).

POLICY

MEDICAL APPROPRIATENESS

IMPORTANT REMINDERS

ADDITIONAL INFORMATION

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.

SOURCES

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

ID_BT

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.

This document has been classified as public information.