Humana Noninvasive Prenatal Testing Form

Description

First trimester noninvasive prenatal testing (NIPT) is usually done between 11 to 14 gestational weeks to check for chromosomal abnormalities and can be completed in a single combined test or in a multistep process. A blood sample, taken from a pregnant woman, is analyzed for free β-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) levels. In addition, an ultrasound may be performed to measure nuchal translucency (thickness of the space between the back of the fetal neck and overlying skin). The results of these tests (and consideration of maternal age) are used to calculate specific risk for fetal chromosomal disorders. If these results demonstrate a significant probability of a fetal abnormality, invasive testing such as amniocentesis or chorionic villus sampling (CVS), may be performed.

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Noninvasive Prenatal Testing Effective Date: 12/14/2023
Revision Date: 12/14/2023
Review Date: 12/14/2023
Policy Number: HUM-0430-034
Page: 2 of 23

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Second trimester NIPT

may include maternal serum testing for alpha-fetoprotein (AFP) levels to check for neural tube defects. This test is generally performed between 16 to 18 weeks of pregnancy. Multiple marker screening (also referred to as triple screen or quad screen) may be performed during the second trimester and includes testing maternal serum levels of AFP, hCG, unconjugated estriol (uE3) and/or inhibin-A to combine screening for chromosome abnormalities and neural tube defects. This panel is usually done around 15 to 20 gestational weeks when abnormal levels could indicate that further evaluation may be needed with invasive testing.

For information regarding prenatal invasive diagnostic genetic testing, please refer to the Prenatal Invasive Diagnostic Genetic Testing Medical Coverage Policy.

For NIPT for Zika virus, please refer to the Centers for Disease Control and Prevention (CDC) for the current guidelines.

Prenatal cell-free deoxyribonucleic acid (cfDNA) noninvasive screening tests

are laboratory studies that examine changes in human DNA, chromosomes, genes or gene products (such as proteins) of cfDNA sequences that are isolated in the maternal plasma during pregnancy. Examples include:

• Genome testing (eg, MaterniT Genome, PreSeek, Resura, VERAgene, Vistara) analyzes fetal chromosomes for extra or missing parts of chromosomes or other whole chromosome changes. (Refer to Coverage Limitations section)
• Sequencing-based trisomy tests for fetal aneuploidy detect chromosome abnormalities. These advanced screening tests are used to detect one or more of the following:
  1. Aneuploidies involving chromosomes 13, 18 and 21
  2. Aneuploidies involving sex chromosomes (Refer to Coverage Limitations section)
  3. Microdeletions/microduplications (Refer to Coverage Limitations section)
  4. Screening for single gene variants (Refer to Coverage Limitations section)
• Screening for twin zygosity (Refer to Coverage Limitations section)

Cell-based NIPT that isolates fetal DNA from rare fetal trophoblast cells, circulating in maternal blood, has also been proposed for prenatal screening and diagnosis.

Noninvasive Prenatal Testing Effective Date: 12/14/2023
Revision Date: 12/14/2023
Review Date: 12/14/2023
Policy Number: HUM-0430-034
Page: 3 of 23

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

This method of testing is purported to detect fetal chromosomal aneuploidy and chromosomal deletions/duplications commonly linked to genetic conditions, as early as 8 weeks gestation. (Refer to Coverage Limitations section)

Pre-eclampsia

is a disorder of pregnancy characterized by the onset of high blood pressure and protein in the urine which typically begins after the twentieth week of pregnancy. Monitoring of maternal blood pressure is routinely used as a screening tool to evaluate for pre-eclampsia during prenatal visits.

Available tests include, but not may not be limited to:

• quantitative placental growth factor [PlGF] in plasma) is to be used in conjunction with the BRAHMS sFlt-1 KRYPTOR (an automated immunofluorescent assay for quantitative soluble fms-like tyrosine kinase-1 [sFlt-1], also known as VEGF receptor-1) along with other laboratory tests and clinical assessments to assess pregnant women (singleton pregnancies 23 to 35 weeks gestation) who have been hospitalized for hypertensive disorders of pregnancy (preeclampsia, chronic hypertension with or without superimposed preeclampsia or gestational hypertension) to purportedly aid in the risk for progression to preeclampsia with severe features. (Refer to Coverage Limitations section)
• Mirvie RNA platform uses RNA analyses and machine-learning to identify pre-eclampsia risk before the clinical presentation of symptoms37 (Refer to Coverage Limitations section)
• PlGF 1-2-3 Assay is a biochemical assay of PlGF, time-resolved fluorescence immunoassay, maternal serum and predictive algorithm that is used as a risk score for preeclampsia40 (Refer to Coverage Limitations section)
• PEPredictDx evaluates a serum specimen for three biomarkers (kinase insert domain receptor, endoglin and retinol-binding protein 4) using immunoassay technique that reports a risk score for preeclampsia PE as early as 11 weeks in pregnancy (Refer to Coverage Limitations section)

Preterm birth

(delivery prior to 37 weeks gestation) occurs in approximately 10% of pregnancies in the United States. The PreTRM test is purported to predict spontaneous preterm birth as early as 19 weeks of gestation in asymptomatic, singleton pregnancies by analyzing multiple maternal serum proteins and other clinical data.41 (Refer to Coverage Limitations section)

Ultrasonography (ultrasound) is commonly used in the second trimester of pregnancy to monitor fetal development and maternal well-being. Two-dimensional (2D) ultrasound may be performed to determine gestational age, number of fetuses, fetal cardiac activity and placental location. In addition, many congenital structural anomalies and significant abnormalities in fetal growth may be identified.

Three-dimensional (3D) ultrasound uses special probes and software to acquire a 2D static display of 3D data. Although the indications for its use have not been well-defined, 3D technology can purportedly reduce scanning time and better demonstrate abnormalities previously detected with 2D sonography including facial abnormalities and neural tube defects. Four-dimensional (4D) ultrasound (also called dynamic 3D sonography) refers to 3D images that can be viewed in real-time. Five-dimensional (5D) ultrasound (also known as high-definition live) includes a software package on the ultrasound unit that purportedly enhances facial skin tone and depth perception through lighting techniques which results in high-resolution images.

Noninvasive Prenatal Testing Effective Date: 12/14/2023
Revision Date: 12/14/2023
Review Date: 12/14/2023
Policy Number: HUM-0430-034
Page: 4 of 23

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

(Refer to Coverage Limitations section) Fetal magnetocardiography is a noninvasive technique for recording magnetic fields generated by the electrical activity of the fetal heart. It is a passive recording technique utilizing high sensitivity Superconducting Quantum Interference Device (SQUID) sensors. These sensors amplify signals that are naturally occurring, yet weak. (Refer to Coverage Limitations section)

Coverage Determination

Any state mandates for noninvasive prenatal screening take precedence over this medical coverage policy.

Humana members may be eligible under the Plan for NIPT for chromosomal abnormalities using ONE of the following:

• Multiple marker screening (inhibin-A, free or total hCG, PAPP-A and/or uE3 levels) with or without 2D ultrasonography* (measurement of nuchal translucency); OR
• Sequencing-based tests in single or twin gestation pregnancies, using cfDNA to screen for fetal trisomy aneuploidy 13, 18 and 21 (81420, 81507, 0327U)

Humana members may be eligible under the Plan for NIPT for neural tube defects performed in the second trimester using 2D ultrasonography* (eg, screening for fetal anomalies) with or without maternal serum AFP. *2D ultrasonography may be performed up to the terms and conditions of the member’s individual certificate.

Note: The criteria for NIPT for chromosomal abnormalities are not consistent with the Medicare National Coverage Policy and therefore may not be applicable to Medicare members. Refer to the CMS website for additional information.

Coverage Limitations

Humana members may NOT be eligible under the Plan for the following NIPT for any indication:

• 3D, 4D or 5D ultrasonography
• Fetal magnetocardiography
• First trimester ultrasound assessment of the nasal bone

These are considered experimental/investigational as they are not identified as widely used and generally accepted for the proposed uses as reported in nationally recognized peer-reviewed medical literature published in the English language.

Humana members may NOT be eligible under the Plan for cfDNA sequence-based prenatal screening for fetal trisomy aneuploidy (13, 18 and 21) (eg, 81420, 81507, 0327U) for any indications other than those listed above in the coverage determination section including, but may not be limited to, the following:

Noninvasive Prenatal Testing Effective Date: 12/14/2023
Revision Date: 12/14/2023
Review Date: 12/14/2023
Policy Number: HUM-0430-034
Page: 6 of 23

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

• Duplicative or repeat (during the same pregnancy) testing for low fetal fraction or test failure); OR
• Duplicative or repeat NIPT testing for chromosomal abnormalities (eg, multiple marker screening with or without 2D ultrasound for nuchal translucency) has been performed during the current pregnancy; OR
• Expanded testing of microdeletion/microduplication analysis (eg, DiGeorge syndrome, Prader-Willi syndrome) (81422); OR
• Screening for monogenic disorders (eg, beta thalassemia, hemophilia, sickle cell anemia); OR
• Screening for sex chromosome aneuploidies; OR
• Screening for single gene variants (eg, known familial variant); OR
• Screening for trisomies other than 13, 18 and 21; OR
• Screening for twin zygosity (0060U); OR
• Testing prior to 10 weeks gestation; OR
• Triplet or higher gestation pregnancies

These are considered experimental/investigational as it is not identified as widely used and generally accepted for any other proposed use as reported in nationally recognized peer-reviewed medical literature published in the English language.

Humana members may NOT be eligible under the Plan for the following NIPT for any indication:

• BRAHMS SFlt-1/ PlGF KRYPTOR Test System; OR
• Luna Prenatal Test (0341U); OR
• MaterniT GENOME; OR

Noninvasive Prenatal Testing Effective Date: 12/14/2023
Revision Date: 12/14/2023
Review Date: 12/14/2023
Policy Number: HUM-0430-034
Page: 7 of 23

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

• Mirvie RNA platform; OR
• PlGF 1-2-3 assay (0243U); OR
• PEPredictDx (0390U); OR
• PreSeek; OR
• PreTRM (0247U); OR
• Resura; OR
• VERAgene; OR
• Vistara

These are considered experimental/investigational as they are not identified as widely used and generally accepted for the proposed uses as reported in nationally recognized peer-reviewed medical literature published in the English language.

Humana members may NOT be eligible under the Plan for NIPT for any indications other than those listed above, including the detection of genetic susceptibility to adult-onset/late-onset disorders. This is considered not medically necessary as defined in the member’s individual certificate. Please refer to the member’s individual certificate for the specific definition.

Fetal sex testing is considered integral to the panel of standard blood tests and is not separately reimbursable.

Individual serum levels (eg, AFP, hCG [duplicate form], inhibin-A, PAPP-A, uE3) reported with multianalyte assays with algorithmic analysis (MAAA) for fetal congenital anomalies (81508, 81509, 81510, 81511, 81512) are not separately reimbursable.

Noninvasive Prenatal Testing Effective Date: 12/14/2023
Revision Date: 12/14/2023
Review Date: 12/14/2023
Policy Number: HUM-0430-034
Page: 8 of 23

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Additional information about fetal chromosomal abnormalities may be found from the following websites:

• Background
• American College of Medical Genetics and Genomics
• American College of Obstetricians and Gynecologists
• National Library of Medicine

Alternatives to screening tests for preeclampsia include, but may not be limited to, the following:

• Medical Alternatives
• Fetal biophysical profile
• Urine analysis

Alternatives to PreTRM include, but may not be limited to, the following:

• Fetal fibronectin testing
• Transvaginal ultrasound exam

Physician consultation is advised to make an informed decision based on an individual’s health needs.

Humana may offer a disease management program for this condition. The member may call the number on his/her identification card to ask about our programs to help manage his/her care.