non-invasive prenatal testing - health alliance€¢ non-invasive prenatal testing (nipt) is...

Non-Invasive Prenatal Testing Procedure(s) covered by this policy:

Procedure Code(s)

Requires: Prior-

authorization* Lab Procedure Restrictions†

Non-Invasive Prenatal Testing for Fetal Aneuploidy 81420 Yes No

Non-Invasive Prenatal Testing for Fetal Aneuploidy with Risk Score 81507 Yes No

Non-Invasive Prenatal Testing for Fetal Aneuploidy with Risk Score 0009M Yes No

Unlisted molecular pathology procedure [when specified as DNA sequencing to detect fetal aneuploidies]

81479 Not Covered Not Covered

Non-Invasive Prenatal Testing for Fetal Aneuploidy 81599 Not Covered Not Covered



* - Clinical Review necessary prior to authorization for this procedure.

† - Lab procedures require specified sequence to be followed and additional information is required to be supplied by lab performing procedure(s).

What Is a Chromosome Abnormality? • Humans usually have 23 pairs of chromosomes. Each chromosome has a

characteristic appearance that should be the same in each person. • A chromosome abnormality is any difference in the structure, arrangement, or

amount of genetic material packaged into the chromosomes.1 • Chromosome abnormalities can lead to a variety of developmental and

reproductive disorders. Common chromosome abnormalities that affect development include Down syndrome (trisomy 21), trisomy 18, trisomy 13, Turner syndrome, and Klinefelter syndrome.

• About 1 in 200 newborns has some type of chromosome abnormality and a higher percentage of pregnancies are affected but lost during pregnancy. About 6%-11% of stillbirths or neonatal deaths are associated with a chromosome abnormality.2,3

• The risk of having a child with an extra chromosome, notably Down syndrome, increases as a woman gets older.3 Historically, invasive prenatal diagnosis was only offered to women over the age of 35. However, many babies with Down syndrome are born to women under 35. Prenatal screening for Down syndrome and certain other chromosome abnormalities is now routinely offered to all pregnant women. As a result, prenatal diagnosis is now an option for most pregnant women.

Lab Management Guidelines

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Test Information • Non-invasive prenatal testing (NIPT) is performed on a maternal plasma sample

collected after approximately 9-10 weeks’ gestation.4 • Testing methodology relies on the presence of cell-free fetal DNA in maternal

circulation.4 Approximately 10% of DNA in maternal circulation is of fetal origin.5 • Analysis of cell-free fetal DNA is performed to identify pregnancies at high risk for

chromosomal aneuploidy. Detection rates for trisomies 21, 18, and 13 are greater than 98%, with false positive rates of less than 0.5%.4

• Some laboratories also test for sex chromosome aneuploidies (such as Turner syndrome or Klinefelter syndrome) as well as rare chromosome microdeletion syndromes, with variable performance.

• Each commercial laboratory offering NIPT has a proprietary platform and bioinformatics pipeline.

• Chromosome analysis on invasive diagnostic testing (CVS and amniocentesis) is also routinely available for assessment of fetal chromosome abnormalities in pregnancy.

Guidelines and Evidence • In 2012, The American College of Obstetricians and Gynecologists (ACOG)

and the Society for Maternal Fetal Medicine (SMFM) jointly recommended cell free fetal DNA (cfDNA) as one option that can be used as a primary screening test in women at increased risk of aneuploidy. 4

o Indications for considering the use of cell free fetal DNA include (directly quoted): Maternal age 35 years or older at delivery Fetal ultrasonographic findings indicating an increased risk of

aneuploidy History of a prior pregnancy with a trisomy Positive test result for aneuploidy, including first trimester,

sequential, or integrated screen, or a quadruple screen Parental balanced Robertsonian translocation with increased risk of

fetal trisomy 13 or 21 o “Cell free fetal DNA testing should not be offered to low-risk women or

women with multiple gestations because it has not been sufficiently evaluated in these groups.”

o “Cell free fetal DNA does not replace the accuracy and diagnostic precision of prenatal diagnosis with CVS or amniocentesis, which remain an option for women.”

• The International Society for Prenatal Diagnosis (ISPD) first issued a position statement on NIPT in January 2011 and then updated its recommendations in April 2013. ISPD summarizes that:6

o NIPT for aneuploidy screening can be helpful for women determined to be high-risk by other screening methods, maternal age, or family history.



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o “Analytic validity trials have been mostly focused on patients who are at high risk on the basis of maternal age or other screening tests. Efficacy in low risk populations has not yet been fully demonstrated.”

o “The tests should not be considered to be fully diagnostic and therefore are not a replacement for amniocentesis and CVS. Some affected pregnancies may not be detected and there may be false-positive results."

o “There is insufficient information to know how well the test will perform in multiple gestation pregnancies that are discordant for trisomy but, theoretically, the detection of affected pregnancies could be lower than in singletons.”

• The National Society of Genetic Counselors (NSGC, 2013) practice guideline includes NIPT as an option for patients at increased risk for chromosome aneuploidy:7

o “Patients who desire screening information may be offered NIPT due to the high detection rates and low false positive rates. NIPT should only be offered in the context of informed consent, education, and counseling by a qualified provider, such as a genetic counselor. Standard confirmatory diagnostic testing should be offered as follow-up to positive NIPT results. High risk patients who decline NIPT but remain interested in screening should be made aware of alternate screening options as appropriate based on gestational age and screening availability.”

• The American College of Medical Genetics and Genomics (ACMG, 2013) published a policy statement regarding Non Invasive Prenatal Screening (NIPS), stating “although studies are promising and demonstrate high sensitivity and specificity with low false positive rates, there are limitations to NIPS.” Due to the limitations outlined in the policy statement, ACMG states that “invasive testing is recommended for confirmation of a positive screening test and should remain an option for patients seeking a definitive diagnosis. In addition to limitations of NIPS, the policy provides clear recommendations for the components of pre- and post-test genetic counseling. The policy statement does not, however, provide guidance regarding to whom NIPS should be offered. 5

• Early evidence for the performance of NIPT in the low-risk population was published by Bianchi and colleagues in the New England Journal of Medicine in February 2014.8 Following this publication, The Society for Maternal Fetal Medicine (SMFM, 2014) reiterated its position that NIPT should be limited to high-risk pregnancies, stating: “SMFM has reviewed the evidence, including this recent paper, and feels that while NIPT is a promising new technology, and this new report is important and excellent news, it is not enough to change current ACOG and SMFM recommendations. Given that just eight aneuploidies were present in the entire cohort of patients, the true test performance is difficult to determine.”9

• The Society for Maternal Fetal Medicine (SMFM, 2015) published an expert opinion on NIPT, reiterating its position regarding the use of NIPT in high-risk pregnancies, while also clearly stating that “routine screening for microdeletions with cfDNA is not recommended.”10



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Criteria • Genetic Counseling:

o Pre and post-test genetic counseling by an appropriate provider (as deemed by the Health Plan policy), AND

• Previous Genetic Testing: o No previous cell free fetal DNA testing already performed during this

pregnancy, and o No previous karyotyping, aneuploidy FISH, and/or array CGH already

performed during this pregnancy, AND • Diagnostic or Predisposition Testing:

o Cell-free fetal DNA-based prenatal screening for fetal aneuploidy (trisomy 13, 18, and 21) is considered medically necessary when all of the following criteria are met: Singleton pregnancy, and Gestational age within the window validated by the selected testing

laboratory, and At least one of the following increased risk indications:

• Advanced maternal age defined as 35 years or older at delivery‡, or

• Abnormal first or second trimester screening result (nuchal translucency or maternal serum) associated with an increased risk for a chromosome abnormality detectable by NIPT, or

• Fetal ultrasound findings that suggest an increased risk for a chromosome abnormality that is detectable by NIPT**, or

• Previous pregnancy with a chromosome abnormality detectable by NIPT‡, or

• Parental chromosome abnormality associated with an increased risk for a chromosome abnormality detectable by NIPT‡ (e.g., balanced Robertsonian translocation of chromosome 13 or 21), AND

o Rendering laboratory is a qualified provider of service per the Health Plan policy.

• Additional testing: o This policy applies to only cell-free fetal DNA-based prenatal screening for

common aneuploidies of chromosomes 13, 18, and 21. o Screening for aneuploidy of the X and Y chromosomes and/or detection of

less common trisomies, are not separately reimbursable under these coverage guidelines.

o Detection of microdeletions by cell-free fetal DNA based screening is not covered.

• Additional prenatal diagnostic testing: o Prenatal diagnosis by amniocentesis or CVS following NIPT is generally

only indicated when NIPT results are abnormal or additional information becomes available throughout the pregnancy that suggests additional risk



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factors. Amniocentesis and/or CVS billed after NIPT are subject to medical necessity review.

‡If conceived by egg and/or sperm donor, these indications must apply to the biological relationship **Prenatal diagnosis by amniocentesis or CVS is recommended when the fetus has a structural birth defect

References 1. Gardner RJM, Sutherland GR. Chromosome Abnormalities and Genetic Counseling (Oxford

Monographs on Medical Genetics, No 29). New York, NY: Oxford University Press; 2004. 2. Robinson A, Lindon MG. Clinical Genetics Handbook. 2nd ed. Cambridge, MA: Blackwell

Scientific Publications; 1993. 3. ACOG Practice Bulletin No. 88, December 2007. Invasive prenatal testing for

aneuploidy. Obstet Gynecol. 2007 Dec; 110(6):1459-67. 4. American College of Obstetricians and Gynecologists Committee on Genetics. Committee

Opinion No. 545: Noninvasive prenatal testing for fetal aneuploidy. Obstet Gynecol. 2012 Dec; 120(6):1532- 4.

5. Gregg A, Gross SJ, Best RG, et al. ACMG statement on noninvasive prenatal screening for fetal aneuploidy. Genet Med. 2013; 15(5):395-8.

6. Wilson KL, Czerwinski JL, Hoskovec JM, et al. NSGC Practice Guideline: Prenatal screening and diagnostic testing options for chromosome aneuploidy. J Genet Counsel. 2013; 22:4-15.

7. 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. 2013; 33(7):622-9.

8. Bianchi DW, Parker RL, Wentworth J, Madankumar R, Saffer C, Das AF, et al; CARE Study Group. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med. 2014 Feb 27; 370(9):799-808.

9. The Society for Maternal-Fetal Medicine press release. SMFM Physicians Recommend NIPT for High-Risk Patients. March 4, 2014. Available at:

10. Society for Maternal-Fetal Medicine (SMFM), SMFM Consult Series #36 Prenatal Aneuploidy Screening using Cell Free DNA, Am J Obstetr Gynecol (2015), doi: 10.1016/j.ajog.2015.03.043

http://www.smfmnewsroom.org/2014/03/smfm-physicians-recommend-nipt-for-high-risk-patients/.



http://www.smfmnewsroom.org/2014/03/smfm-physicians-recommend-nipt-for-high-risk-patients/�

http://www.smfmnewsroom.org/2014/03/smfm-physicians-recommend-nipt-for-high-risk-patients/�

non-invasive prenatal testing - health alliance€¢ non-invasive prenatal testing (nipt) is...

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