4.01.21 noninvasive prenatal screening for fetal ... · pdf filenoninvasive prenatal screening...
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MEDICAL POLICY 4.01.21
Noninvasive Prenatal Screening for Fetal Aneuploidies and
Microdeletions Using Cell-Free Fetal DNA
BCBSA Ref. Policy: 4.01.21
Effective Date: Oct. 1, 2017
Last Revised: March 9, 2018
RELATED MEDICAL POLICIES:
12.04.116 Invasive Prenatal (Fetal) Diagnostic Testing
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POLICY CRITERIA | DOCUMENTATION REQUIREMENTS | CODING
RELATED INFORMATION | EVIDENCE REVIEW | REFERENCES | APPENDIX | HISTORY
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Chromosomes are found in each cell and hold all of the genetic material the DNA of each
person. Each cell usually contains 23 pairs of chromosomes, including the pair that determines
the persons sex. Having more or fewer chromosomes known as aneuploidy results in birth
defects. Screening for aneuploidies is recommended during pregnancy. In the past, this
screening was typically done by examining cells from the fetus. The cells were obtained either by
taking a sample of the placenta or the amniotic fluid surrounding the baby. Newer tests that
require only a blood sample from the mother can be used to screen for aneuploidies. This test
looks at pieces of the fetuss DNA thats naturally circulating in the mothers blood. This policy
describes when this type of blood test may be medically necessary. This blood test is
investigational unproven when its used to look for missing pieces of chromosomes that
are too small to be seen without a microscope. Its also investigational when its used early in the
pregnancy to look at the sex chromosomes.
Note: The Introduction section is for your general knowledge and is not to be taken as policy coverage criteria. The
rest of the policy uses specific words and concepts familiar to medical professionals. It is intended for
providers. A provider can be a person, such as a doctor, nurse, psychologist, or dentist. A provider also can
be a place where medical care is given, like a hospital, clinic, or lab. This policy informs them about when a
service may be covered.
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Policy Coverage Criteria
Testing Medical Necessity Trisomy 21 Nucleic acid sequencingbased testing of maternal plasma
(MaterniT21, verifi, Harmony, Panorama) for trisomy 21
may be considered medically necessary in women with
singleton pregnancies undergoing screening for trisomy 21.
Trisomy 13 and/or 18 Concurrent nucleic acid sequencingbased testing of maternal
plasma for trisomy 13 and/or 18 may be considered medically
necessary in women who are eligible for and are undergoing
nucleic acid sequencingbased testing of maternal plasma for
Testing Investigational Trisomy 21 Nucleic acid sequencingbased testing of maternal plasma for
trisomy 21 is considered investigational in women with twin or
Trisomy 13 and/or 18 Nucleic acid sequencingbased testing of maternal plasma for
trisomy 13 and/or 18, other than in the situations specified
above, is considered investigational.
Fetal sex chromosome
Nucleic acid sequencingbased testing of maternal plasma for
fetal sex chromosome aneuploidies is considered
Microdeletions Nucleic acid sequencing-based testing of maternal plasma for
microdeletions is considered investigational.
Documentation Requirements The patients medical records submitted for review for all conditions should document that
medical necessity criteria are met. The record should include the following:
Documentation of singleton pregnancy
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CPT 0009M Fetal aneuploidy (trisomy 21 and 18) DNA sequence analysis of selected regions using
maternal plasma, algorithm reported as a risk score for each trisomy
81420 Fetal chromosomal aneuploidy (eg, trisomy 21, monosomy X) genomic sequence
analysis panel, circulating cell-free fetal DNA in maternal blood, must include analysis
of chromosomes 13, 18 and 21
81422 Fetal chromosomal microdeletion(s) genomic sequence analysis (eg, DiGeorge
syndrome, Cri-du-chat syndrome), circulating cell-free fetal DNA in maternal blood
81479 Unlisted molecular pathology procedure
81507 Fetal aneuploidy (trisomy 21, 18, and 13) DNA sequence analysis of selected regions
using maternal plasma, algorithm reported as a risk score for each trisomy
81599 Unlisted chemistry procedure
84999 Unlisted chemistry procedure
Note: CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA). HCPCS
codes, descriptions and materials are copyrighted by Centers for Medicare Services (CMS).
This policy refers to non-invasive testing and does not apply to pregnancies with a high clinical
suspicion of fetal microdeletions for which invasive confirmatory testing is indicated (see
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 for fetal aneuploidies, including the option of no
Studies published to date on non-invasive prenatal screening for fetal aneuploidies 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. 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
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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.
As noted in the 2015 ACOG committee opinion, cell-free DNA screening does not assess the 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.
In some cases, tissue samples from chorionic villous sampling (CVS) or amniocentesis may be
insufficient for karyotyping; confirmation by specific fluorescent in situ hybridization (FISH) assay
is acceptable for these samples.
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 one chromosome. The most
important risk factor for trisomy syndromes is maternal age. The approximate risk of a trisomy
21 (T21; Down syndrome)affected birth is 1 in 1100 at age 25 to 29. The risk of a fetus with T21
(at 16 weeks of gestation) is about 1 in 250 at age 35 and 1 in 75 at age 40.1
T21 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,
although the percentage of cases surviving to birth is low and survival beyond birth is limited.
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 T18 and 1T3 are unclear, because survival beyond birth is
limited for both conditions.
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Fetal Aneuploidy Screening
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.2 Standard aneuploidy screening involves combinations of maternal serum markers and
fetal ultrasound done at various stages of pregnancy. 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 T21, T18, and T13 could improve outcomes.
Confirmation of positive noninvasive screening tests with amniocentesis or CVS is
recommended; with more accurate t