Medical Policy: 02.04.38
Original Effective Date: February 2016
Reviewed: February 2017
Revised: February 2017
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This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
Fetal chromosomal abnormalities occur in approximately 1 in 160 live births. Most fetal abnormalities are aneuploidies, defined as an abnormal number of chromosomes, which are the structures that contain genetic information. The trisomy syndromes are aneuploidies involving 3 copies of 1 chromosome, trisomies 21 (Down syndrome), 18 (Edwards syndrome), and 13 (Patau syndrome) are the most common aneuploidies. Trisomy 21 is the most frequent occurring, followed by trisomy 18 then trisomy 13. A risk of having a baby with Down syndrome increases with maternal age, significantly after age 35. However, age cannot serve as the sole screening factor as a high percentage of Down syndrome babies are born to women under the age of 35.
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. 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 trisomy syndrome, direct karyotyping of fetal tissue obtained by amniocentesis or chronic 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 tests, fewer geno typical women could receive positive screening results.
Commercial, noninvasive, sequencing based testing of maternal serum for fetal trisomy syndromes is now available. The test technology involves detection of fetal cell free DNA fragments present in the plasma of pregnant women. As early as 8 to 10 weeks of gestation, these fetal DNA fragments comprise 6% to 10% or more of the total cell-free DNA in a maternal plasma sample. The test are unable to provide a result if fetal fraction is too low, that is, below about 4%. Fetal fraction can be affected by maternal and fetal characteristics. For example, fetal fraction was found to be lower at higher maternal weights and higher with increasing fetal crown-rump length.
Sequencing-based tests, also referred to as noninvasive prenatal testing (NIPT) has been investigated as a method of detecting common fetal aneuploidy including trisomies 21, 18 and 13 in high risk pregnancies (e.g. advanced maternal age, abnormal fetal ultrasound). This testing method relies on the presence of circulating fetal or cell-free DNA in the maternal plasma during pregnancy.
Sequencing-based tests use 1 to 2 general approaches to analyzing cell-free DNA. The first category of tests uses quantitative or counting methods. The most widely used technique to date uses massively parallel sequencing (MPS; also known as next-generation or “next gen” sequencing). DNA fragments are amplified by polymerase chain reaction; during the sequencing process, the amplified fragments are spatially segregated and sequenced simultaneously in a massively parallel fashion. Sequenced fragments can be mapped to the reference human genome to obtain numbers of fragment counts per chromosome. The sequencing-derived percent of fragments from the chromosome of interest reflects the chromosomal representation of the maternal and fetal DNA fragments in the original maternal plasma sample. Another technique is direct DNA analysis, which analyzes specific cell-free DNA fragments across samples and requires approximately a tenth the number of cell-free DNA fragments as MPS. The digital analysis of selected regions (DANSR™) is an assay that uses direct DNA analysis.
The second general approach is single nucleotide polymorphism (SNP) â€’ based methods. These use targeted amplification and analysis of approximately 20,000 SNPs on selected chromosomes (e.g., 21, 18, 13) in a single reaction. A statistical algorithm is used to determine the number of each type of chromosome.
No studies were identified that provided direct evidence on analytic validity. Each of the commercially available tests use massively parallel sequencing (MPS; also called next-generation sequencing [NGS]), a relatively new technology but not an entirely new concept for the clinical laboratory. Currently, there are no recognized standards for conducting clinical sequencing by MPS. On June 23, 2011, the U.S. Food and Drug Administration (FDA) held an exploratory, public meeting on MPS, in preparation for an eventual goal of developing “a transparent evidence-based regulatory pathway for evaluating medical devices/products based on next generation sequencing, NGS, that would assure safety and effectiveness of devices marketed for clinical diagnostics.” The discussion pointed out the difference among manufacturers’ sequencing platforms and the diversity of applications, making it difficult to generate specific regulatory phases and metric. It was suggested that “the process may need to be judged by the accuracy and fidelity of the final result.” A consistent discussion trend was that validation be application specific. Thus, technical performance may need to be more closed linked to intended use and population and may not be generalizable across all sequencing applications. Each of the companies currently offering a maternal plasma DNA sequencing test has developed a specific procedure for its private, Clinical Laboratory Improvement Act-licensed laboratory where all testing takes place.
Although all currently available commercial tests use MPS, actual performance and interpretive procedures vary considerably. Clinical sequencing in general is not standardized or regulated by Food and Drug Administration or other regulatory agencies, and neither the routine quality control procedures used for each of these tests, nor the analytic performance metrics have been published.
The 2013 and 2014 BlueCross BlueShield Association TEC Assessments each constructed decision models to predict health outcomes of sequencing-based testing compared with standard testing. The model in the 2013 TEC assessment focused on T21. In this model, the primary health outcomes of interest included the number of cases of aneuploidy correctly identified, number of cases missed, number of invasive procedures potentially avoided (ie, with a more sensitive test), and the number of miscarriages potentially avoided as a result of fewer invasive procedures. The results were calculated for a high-risk population of women age 35 years or older (estimated antenatal prevalence of T21, 0.95%), and an average-risk population including women of all ages electing an initial screen (estimated antenatal prevalence of T21, 0.25%). For women testing positive on initial screen and offered an invasive, confirmatory procedure, it was assumed that 60% would accept amniocentesis or CVS. Sensitivities and specificities for both standard and sequencing-based screening tests were varied to represent the range of possible values; estimates were taken from published studies whenever possible.
According to the model results, sequencing-based testing improved outcomes for both high-risk and average-risk women. As an example, assuming there are 4.25 million births in the United States per year and two-thirds of the population of average-risk pregnant women (2.8 million) accepted screening, the following outcomes would occur for the 3 screening strategies under consideration:
The model in the 2014 TEC Assessment included T13 and T18 (but not sex chromosome aneuploidies, due to the difficulty of defining relevant health outcomes). The model was similar but not identical to that previously used to evaluate T21. As in earlier model, outcomes of interest included the number of cases of aneuploidy correctly detected and the number of cases missed, and findings were calculated separately for a high-risk population of women aged 35 or older and a low-risk population. The model assumed that 75% of high-risk and 50% of low-risk women who tested positive on the initial screen would proceed to an invasive test. (The T21 model assumed a 60% uptake rate of invasive confirmatory testing.) A distinctive feature of the 2014 modelling study was that it assumed screening for T21 was done concurrently to screening for T13 and T18 and that women who choose invasive testing do so because of a desire to detect T21. Consequently, miscarriages associated with invasive testing were not considered an adverse effect of T13 or T18 screening.
The model compared 2 approaches to screening: (1) a positive sequencing-based screen followed by diagnostic invasive testing; and (2) a positive standard noninvasive screen followed by diagnostic invasive testing. As in the T21 modelling study, sensitivities and specificities for both standard and sequencing-based screening tests were varied to represent the range of possible values; estimates were taken from published studies whenever possible. Assuming that a hypothetical population of 100,000 pregnant women was screened, the model had the following findings:
Results of the modeling suggest that sequencing-based tests detect a similar number of T13 and T18 cases and miss fewer cases than standard noninvasive screening. Even in a hypothetical population of 100,000 women, however, the potential number of detectable cases is low, especially for T13 and for low-risk women.
Modeling studies using published estimates of diagnostic accuracy and other parameters predict that sequencing-based testing as an alternative to standard screening will lead to an increase in the number of Down syndrome cases detected and, when included in the model, a large decrease in the number of invasive tests and associated miscarriages. The number of T18 and T13 cases detected is similar or higher with sequencing-based testing, although this is more difficult to estimate because of the lower prevalence of these aneuploidies, especially with T13. The impact of screening for sex chromosome aneuploidies has not been modeled in published studies.
The available evidence in the published peer reviewed medical literature evaluating the accuracy of clinical utility of sequencing circulating cell-free DNA testing for chromosomal abnormalities consists of validation and cohort studies. These studies have primarily included pregnant women at increased risk for fetal aneuploidy. Fewer studies have been published on maternal plasma DNA sequencing-based tests for detection of T21 in average risk women. The studies conducted in average risk women identified a small number of trisomies and did not confirm negative or positive findings in all cases. Therefore, the evidence of accuracy of sequencing based testing is less definitive for women with average risk pregnancies as it is for women with high risk pregnancies.
Regardless of the method, the accuracy of screening for aneuploidy is limited in multiple gestations. With any method based on maternal blood (serum analytes of DNA), only a single composite result for the entire gestation is provided, with no ability to distinguish a differential risk between fetuses. The data regarding the performance of cell-free DNA screening in twin gestations are limited. Although preliminary findings suggest that this screening is accurate, larger prospective studies and published data are needed before this method can be recommended for multiple gestations. Cell-free DNA is not recommended for geno typical women with multiple gestations. There are no available data on higher-order multiples.
There is sufficient evidence in the published, peer reviewed medical literature demonstrating the accuracy and clinical utility of cell-free fetal DNA or sequencing based trisomy testing for maternal blood for the detection of chromosomal abnormalities in a subset of women with a pregnancy at high risk for aneuploidy. Although studies have not addressed improved health outcomes associated with this testing, results obtained from cell-free fetal DNA testing can be used to guide decisions regarding the necessity of invasive testing. With consistently high (i.e. 99% - 100%) sensitivity, specificity, and negative predictive values, no further test is indicated for negative test result. A positive test result does require confirmatory follow-up with amniocentesis or chronic villus sampling. Cell-free fetal DNA testing for aneuploidy has been proven to be accurate and resproducible in the population of women with pregnancies at high risk for aneuploidy. However further well-designed clinical trials are needed to further define the role of this testing in routine pregnancy management as compared to the current standard evaluation of serum biomarkers with or without ultrasonic measurement of nuchal translucency, followed by invasive testing as indicated. Currently the quality and quantity of evidence does not support the use of cell-free fetal DNA testing for pregnancies at average risk for aneuploidy or multiple gestations. Therefore the use of cell-free fetal DNA testing for high risk singleton pregnancies would be considered medically necessary and the use of cell free fetal DNA testing for all other indications to include average risk singleton pregnancies would be considered investigational.
The findings of a decision analysis study included in the 2014 BlueCross BlueShield Association TEC assessment suggest similar rates of T13 and T18 detection to standard noninvasive screening; the analysis assumed that T13 and T18 screening would be done in conjunction with the T21 screening. Due to low survival rate, the clinical benefit of identifying trisomy 18 and 13 are unclear. Therefore, NIPT using cell-free DNA for T18 and T13 are considered medically necessary in women who are eligible for and are undergoing testing of maternal plasma for T21 and investigational otherwise.
The data regarding the performance of NPIT using cell-free DNA screening in twin gestations are limited. Although preliminary findings suggest that this screening is accurate, larger prospective studies and published data are needed before this method can be recommended for multiple gestations. Cell-free DNA is not recommended for women with multiple gestations and there is no available data on higher-order multiples.
Therefore, the evidence is insufficient to determine the effects of this technology on net health outcomes and is considered investigational.
Some of the commercially available cell-free DNA prenatal tests also test for other abnormalities including sex chromosome abnormalities and selected microdeletions.
Microdeletions (also known as submicroscopic deletions) are defined as chromosomal deletions that are too small to be detected by microscopy or conventional cytogenetic methods. They can be as small as 1 and 3 megabases (mb) long. Microdeletions, along with microduplications, are collectively known as copy number variations (CNVs). CNVs can lead to disease when the change in copy number of a dose-sensitive gene or genes disrupts the ability of the gene(s) to function and effects the amount of protein produced. A number of genomic disorders associated with microdeletions have been identified. The disorders have distinctive and, in many cases, serious clinical features, such as cardiac anomalies, immune deficiency, palatal defects and developmental delay. Examples of microdeletion syndromes include: DiGeorge syndrome or velocardiofacial syndrome (most common), Prader-Willi syndrome, Angelman syndrome, Neurofibromatosis type I, Neurofibromatosis type II, Williams syndrome, Miller-Dieker syndrome, Smith-Magenis syndrome, Rubinstein-Taybi syndrome and Wolf-Hirschhorn syndrome.
Proportion of microdeletions are inherited and some are de novo. Accurate estimates of the prevalence of microdeletion syndromes during pregnancy or at birth are not available. Risk of fetus with a microdeletion syndrome is independent of maternal age. There is little population based data and most studies published to date base estimates on phenotypic presentation. The 22q11.2 (DiGeorge) deletion is the most common microdeletion associated with a clinical syndrome.
Routine prenatal screening for microdeletion syndromes is not recommended by national organizations. Current practice is to offer invasive prenatal diagnostic testing in selected cases to women with prenatal ultrasound indicates anomalies (e.g. heart defects, cleft palate) that could be associated with a particular microdeletion syndrome. Samples are analyzed using fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA) or karyotyping. In addition, families at risk, those known to have the deletion or with a previous affected child generally receive genetic counseling. Most affected individuals are identified postnatally based on clinical presentation and may be confirmed with genetic testing.
Microdeletion testing is currently offered commercially by 2 companies. Several studies on clinical validity of microdeletion testing have been published, based on large numbers of samples submitted to the testing companies. These studies have limitations (e.g. substantial missing data on confirmatory testing, lack of complete data on false negatives). Many of the cases of microdeletion syndromes are currently initially detected via characteristic anomalies seen on prenatal ultrasound.
The clinical utility of testing for any particular microdeletion or any panel of microdeletions is uncertain. There is no direct data on whether sequencing-based testing for microdeletions improve outcomes compared with standard care. The incidence of microdeletions in otherwise normal pregnancies is extremely low, lower than the threshold level of testing established for carrier testing (generally 1%). Further, the incidence of clinical disease is likely lower than the incidence of microdeletion mutations because not all individuals with a microdeletion will have clinical symptoms. Thus, the yield of testing is very low, requiring testing of many patients to identify a small number of cases.
There is a potential that prenatal identification of individuals with microdeletion syndromes could improve health outcomes due to the ability to allow for informed reproductive decision making, and/or to initiate earlier treatment; however data demonstrating improvement are unavailable. Given the variability of expressivity of microdeletion syndromes and the lack of experience with routine genetic screening for microdeletions, clinical decision making based on genetic test results is not well defined. It is not clear what follow-up testing or treatments might be indicated for screen-detected individuals. Routine prenatal screening may identify a small percentage of fetuses with microdeletion mutations earlier in pregnancy than would otherwise have occurred (eg, by ultrasound evaluation and diagnostic testing). At the same time, routine prenatal screening for microdeletions would also result in false-positive tests and a larger number of invasive confirmatory tests. The large number of confirmatory tests could lead to a net harm as a result of pregnancy loss.
The clinical utility of NIPS for microdeletions remains unclear and has not been evaluated in published studies. The incidence of microdeletions syndromes is low, and not all individuals with microdeletion have clinical symptoms. Clinical follow-up of screen detected microdeletions is unclear and screening has potential associated harms (e.g. pregnancy loss associated with confirmatory tests for positive screens). Given the gaps in the evidence, conclusions cannot be drawn about the impact of this testing on net health outcomes.
Sex chromosome aneuploidies belong to a group of genetic conditions that are caused or affected by the loss or damage of sex chromosomes (genosomes). This may refer to: 47, XXX; 48, XXXX; 49 XXXXY syndrome; 49, XXXXX; Klinefelter’s syndrome, XXY; Turner syndrome, X; XXX gonadal dysgenesis; XX male syndrome; XXYY syndrome; XYY syndrome. These aneuploidies are typically diagnosed postnatally, sometimes not until adulthood, such as during an evaluation of diminished fertility. Alternatively, sex chromosome aneuploidies may be diagnosed incidentally during invasive karyotype testing of pregnant women at high risk for Down syndrome. Potential benefits of early identification (e.g. the opportunity for early management of the manifestations of the condition), must be balanced against potential harms that can include stigmatization and distortion of a family’s view of the child.
The evidence for NIPS using cell free DNA to detect sex chromosome aneuploidies in individuals pregnant with singletons includes several diagnostic studies. There is less published evidence on the diagnostic performance of sequencing-based tests for detecting fetal sex chromosome anomalies, and most of the available studies were conducted in high-risk pregnancies. Meta-analyses of available data suggests high sensitivities and specificities, but the small number of cases, especially for T13, makes definitive conclusions difficult. The evidence is insufficient to determine the effects of this testing on net health outcomes.
Counseling regarding the limitations of cell-free DNA should include a discussion about how the screening methods provide information regarding only trisomies 13, 18, and 21. If a sex chromosome analysis has been requested or is part of the standard panel, then this information should be conveyed as well.
Patients should be counseled that cell-free DNA screening does not replace the precision obtained with diagnostic tests, such as chronic villus sampling or amniocentesis and, therefore, is limited in its ability to identify all chromosome abnormalities. Not only can there be false-positive test results, but a positive cell-free DNA test result for aneuploidy does not determine if the trisomy is due to a translocation, which affects the risk of recurrence. If a fetal structural anomaly is identified on ultrasound examination, diagnostic testing should be offered rather than cell-free DNA screening.
The cell-free DNA screening test should not be considered in isolation from other clinical findings and test results. Given the potential for inaccurate results and to understand the type of trisomy for recurrence-risk counseling, a diagnostic test should be recommended for a patient who has a positive cell-free DNA test result. Management decisions, including termination of the pregnancy, should not be based on the results of the cell-free DNA screening alone. False-positive results do occur and diagnostic testing with amniocentesis or chronic villus sampling (CVS) should be recommended before any pregnancy termination decision. Causes of false-positive test results have been reported, which include but are not limited to placental mosaicism, vanishing twins, and maternal malignancies.
Before offering cell-free DNA screening, counseling is recommended. The family history should be reviewed to determine if the patient should be offered other forms of screening or prenatal diagnosis for a particular disorder. In order to ensure accuracy and testing of the appropriate patient population, a baseline ultrasound examination also should be considered to confirm viability, the number of fetuses, and gestational dating, if not performed previously. Patients should be counseled that a negative cell-free DNA test result does not ensure an unaffected pregnancy. A negative test result still carries a residual risk of one of the common trisomies and does not ensure that the fetus does not have another chromosome abnormality or genetic diagnosis. Cell-free DNA screening does not assess risk of fetal anomalies such as neural tube defects or ventral wall defects. Patients who are undergoing cell-free DNA should be offered maternal serum alpha-fetoprotein screening or ultrasound evaluation for risk assessment. Parallel or simultaneous testing with multiple screening methodologies for aneuploidy is not cost effective and should not be performed. However, use of cell-free DNA screening as a follow-up test for patients with positive traditional screening test is reasonable for patients who want to avoid a diagnostic test.
Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the Clinical Laboratory Improvement Act (CLIA). Laboratories that offer LDTs must be licensed by CLIA for high complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of noninvasive prenatal screening tests using cell-free fetal DNA. Commercially available tests include but are not limited to the following:
In 2012, The American College of Obstetricians and Gynecologists issued a committee opinion, number 545 for noninvasive prenatal testing for fetal aneuploidy that included the following indications for considering the use of cell-free fetal DNA:
September 2015, ACOG and the Society of Maternal Fetal Medicine related an updated committee opinion (number 640) on cell-free DNA screening for fetal aneuploidy (this document replaces committee opinion number 545). The list of recommendations in the 2015 committee opinion includes the following:
In 2015, the public and professional policy committee of the European Society of Human Genetics and the social issues committee of the American Society of Human Genetics issued a joint statement on NIPS (also called noninvasive prenatal testing [NIPT]). Relevant recommendations are as follows:
In 2013, the National Society of Genetic Counselors (NSGC) published a position statement on NIPS of cell-free DNA in maternal plasma. NSGC supports noninvasive cell-free DNA testing as option in women who want testing for aneuploidy. The document states that the test has been primarily validated in pregnancies considered to be at increased risk of aneuploidy, and the organization does not support routine first-tier screening in low-risk populations. In addition, the document states that test results should not be considered diagnostic, and abnormal findings should be confirmed through conventional diagnostic procedures, such as chronic villous sampling (CVS) and amniocentesis.
In 2013, the American College of Medical Genetics and Genomics (ACMG) published a statement on noninvasive prenatal screening for fetal aneuploidy that addresses challenges in incorporating noninvasive testing into clinical practice. Limitations identified include that chromosomal abnormalities such as unbalanced translocations, deletions and duplications, single-gene mutations, and neural tube defects cannot be detected by the new tests. Moreover, it currently takes longer to obtain test results than with maternal serum analytes. ACMG also stated that pretest and posttest counseling should be performed by trained personnel.
In 2016, the American College of Medical Genetics and Genomics (ACMG) published updated position statement regarding noninvasive prenatal screening for fetal aneuploidy.
Should noninvasive prenatal screening (NIPS) be offered to all patients including those at low or average risk?
Should NIPS be used to screen for autosomal aneuploidies other than Patau, Edwards, and Down Syndromes?
Should NIPS be offered to screen for sex chromosome aneuploidies?
Should NIPS be offered for detection of copy number variation (CNV)?
Special Considerations - multiple gestation and/or donor oocytes
In 2015, the International Society for Prenatal Diagnosis published a position statement on prenatal diagnosis of chromosomal abnormalities, an update of their 2013 statement.34,35 (Note that a number of the authors of the 2015 report had financial links to industry.) Following is the summary of recommendations:
Noninvasive prenatal testing (NPIT) using cell free fetal DNA of maternal plasma (including but not limited to the following: MarterniT21, MaterniT21 Plus, Verifi Prenatal Test, Harmony Prenatal Test, Panorama Prenatal Test, QNatal Advanced and InformSeqSM) for fetal aneuploidy (trisomy 13, 18 and 21) is considered medically necessary in women with high – risk singleton pregnancies meeting the following criteria:
Maternal age 35 years or older at delivery; or
Fetal ultrasound findings indicate an increased risk of aneuploidy*; or
History of prior pregnancy with aneuploidy (trisomy); or
Positive test result for aneuploidy, including first trimester, sequential, or integrated screen, or a quadruple screen; or
Parental balanced robertsonian translocation with increased risk of fetal trisomy 13 or trisomy 21
Note: See Policy Guidelines for ultrasound findings criteria indicating increased risk for aneuploidy.*
Concurrent noninvasive prenatal testing (NPIT) using cell free fetal DNA of maternal plasma for trisomy 13 and/or 18 may be considered medically necessary in women who are eligible and undergoing noninvasive prenatal testing (NPIT) using cell free fetal DNA of maternal plasma for trisomy 21.
Noninvasive prenatal testing (NPIT) using cell free fetal DNA of maternal plasma for trisomy 13 and/or 18, other than in the situation specified above, is considered investigational because the safety and/or effectiveness cannot be established based on review of available peer reviewed medical literature.
Noninvasive prenatal testing (NPIT) using cell free fetal DNA of maternal plasma for fetal aneuploidy (trisomy 13, 18, 21) is considered investigational in women with average/low risk singleton pregnancies, twin or multiple pregnancies.
Cell-free fetal DNA testing for aneuploidy has been proven to be accurate and reproducible in the population of women with pregnancies at high risk for aneuploidy. However further well-designed clinical trials are needed to further define the role of this testing in routine pregnancy management as compared to the current standard evaluation of serum biomarkers with or without ultrasonic measurement of nuchal translucency, followed by invasive testing as indicated. Currently the quality and quantity of evidence does not support the use of cell-free fetal DNA testing for singleton pregnancies at average/low risk for aneuploidy. Therefore the use of cell-free fetal DNA testing average/low risk singleton pregnancies is considered investigational.
The data regarding the performance of NPIT using cell-free DNA screening in twin and multiple gestations are limited. Although preliminary findings suggest that this screening is accurate, larger prospective studies and published data are needed before this method can be recommended for twin or multiple gestations. Cell-free DNA is not recommended for women with twin gestations and there is no available data on higher-order multiples. Therefore, the evidence is insufficient to determine the effects of this technology on net health outcomes and is considered investigational.
Noninvasive prenatal testing (NPIT) using cell free fetal DNA of maternal plasma for fetal sex chromosome aneuploidies is considered investigational because the safety and/or effectiveness cannot be established based on review of available peer reviewed medical literature.
Noninvasive prenatal testing (NPIT) using cell free fetal DNA of maternal plasma for microdeletions is considered investigational because the safety and/or effectiveness cannot be established based on review of available peer reviewed medical literature.
Trisomy 21 (Down syndrome) — Approximately one-third of fetuses with trisomy 21 have one or more sonographically detectable structural malformations (major or minor) in the following systems:
Trisomy 18 — After Down syndrome, trisomy 18 is the second most common autosomal trisomy detected in the second trimester; it is almost always lethal in early childhood). Sonographic abnormalities include:
Trisomy 13— Trisomy 13 is rare (incidence 1/5,000 to 1/20,000 births) and associated with more severe structural malformations than trisomy 21 or 18. It is sonographically detectable in >90 percent of cases due to the presence of multiple, severe structural malformations, including:
Average/Low Risk Pregnancy: No active complications and that there are no maternal or fetal factors that place the pregnancy at increased risk for complications.
Aneuploidy: an abnormal number of chromosomes in the cell. Except for red blood cells and the sperm and egg cells, every cell in the human body has 23 pairs of chromosomes (for a total of 46).
Translocation: A translocation occurs when a segment of genetic material from one chromosome becomes linked to another chromosome:
Trisomy: three copies of a chromosome are present instead of the usual pairs. Syndromes associated with trisomies include:
To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or ICD diagnosis codes.
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