Test Catalog

Test ID: NIPS    
Cell-Free DNA Prenatal Screen, Blood

Useful For Suggests clinical disorders or settings where the test may be helpful

Noninvasive screening for aneuploidies of chromosomes 13, 18, and 21 in pregnancies

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This is noninvasive prenatal screening for aneuploidies in pregnancies.


Prior Authorization is available for this assay; see Special Instructions.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test is only available to clients in North and South America.


When this test is ordered, additional statistical analysis to determine the percentage of fetal DNA present is always performed.


The following algorithms are available in Special Instructions:

-Prenatal Aneuploidy Screening and Diagnostic Testing Options

-High-Risk Pregnancy Based on Abnormal Fetal Malformations: Laboratory Testing Algorithm

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

This test provides the ability to detect common chromosome abnormalities, specifically aneuploidy including Down syndrome (trisomy 21), Patau syndrome (trisomy 13), and Edward syndrome (trisomy 18), without the risk of pregnancy loss associated with invasive prenatal procedures. Chromosomal aneuploidy is the leading known genetic cause of miscarriage and congenital birth defects.


This fetal DNA screen is not a diagnostic test; therefore, abnormal results should be confirmed with invasive prenatal diagnostic testing (such as chorionic villi sampling or amniocentesis) and a genetic consultation is recommended. In addition, a negative result does not ensure an unaffected pregnancy. The false-negative rate for trisomy 21 is less than 1%, for trisomy 18 is 3.6%, and for trisomy 13 is 9.4%.(1) The positive predictive value in low-risk pregnancies is lower than in pregnancies at high risk for aneuploidy.(2)

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

Normal representation of material from chromosomes 13, 18, and 21 will be reported as normal, indicating a low risk for trisomy 13, trisomy 18, and trisomy 21 in the fetus. Fetal sex will be reported. If Y chromosome material is detected, this is suggestive of a male fetus. If Y chromosome material is not detected, this is suggestive of a female fetus.


Increased amounts of chromosomal material will be reported as positive for having a trisomy of the identified chromosome for chromosomes 13, 18, or 21. 

While most specimens undergoing this analysis can be readily characterized, on rare occasions equivocal or incidental results such as aneuploidy of chromosomes other than 13, 18, and 21 as well as other genomic unbalanced rearrangements, may not allow for standard interpretation of this aneuploidy screen. In these situations, a new maternal blood specimen may be requested or a recommendation for other screening measures or diagnostic cytogenetic testing will be made.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

A positive result is not diagnostic of a chromosome abnormality. Likewise, a negative result does not ensure an unaffected pregnancy. Gender cannot be guaranteed based on the presence or absence of Y chromosome material alone. In some instances, results will not be obtained due to the specimen or processing difficulties or the presence of low fetal fraction.


While results of this screen are highly accurate, false-positive or false-negative results may occur due to placental, maternal, or fetal mosaicism, as well as other causes. Cell-free DNA screening does not replace the accuracy and precision of invasive prenatal cytogenetic testing via chorionic villus sampling or amniocentesis.


The laboratory will accept specimens from low-risk pregnancies, but the positive predictive value may be lower and insurance may not cover screening.


The laboratory will accept specimens from multiple gestations (twins, etc) but the positive predictive value may be lower and this will be indicated in the interpretation. The laboratory requires that the number of fetuses be reported in order to use the appropriate interpretation.


The laboratory will accept specimens from individuals who are pregnant through the use of donor embryos, donor eggs, or are gestational carriers. It is not currently known how this may affect results. The laboratory should be notified of these situations for submitted patient samples to properly interpret results.


Cell-free DNA screening is validated for use in ongoing viable pregnancies; testing submitted from confirmed cases of miscarriage or fetal demise will be cancelled. For information on diagnostic cytogenetic testing on products of conception, see CMAPC / Chromosomal Microarray, Autopsy/Products of Conception/Stillbirth.


Supportive Data

The accuracy of this assay was assessed by testing 257 specimens. Average maternal age was 34.9 years of age (range of 17.5 to 46.6 years, median 36 years) and average gestational age was 15 weeks (range of 10 to 36 weeks, median 13 weeks). Of these, there were 42 positive samples with a known trisomy of chromosomes 13(n=11), 18(n=21), or 21(n=10), as well as 215 negative samples (as determined by noninvasive prenatal screening by an outside clinical laboratory). Of the 257 samples, the associated fetal sex was: 118 female, 117 male, and 22 samples for which no fetal sex was provided. Of the 135 samples for which fetal sex was provided, all fetal sex calls were concordant. Once filtered for samples not meeting quality control metrics (10 samples), unacceptably low fetal fractions (35 samples), and those for which no call could be determined (10 samples), the sensitivity, specificity, positive predictive value, and negative predictive value were all 100%.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Gil MM, Quezada MS, Revello R, et al: Analysis of cell-free DNA in maternal blood in screening for fetal aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol 2015;45:249-266

2. ACOG/SMFM Joint Committee Opinion: Noninvasive prenatal testing for fetal aneuploidy. No. 640, Dec 2015

3. Bianchi DW, Parker RL, Wentworth J, et al: DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med 2014 Feb;370:799-808

4. Devers PL, Cronister A, Ormond KE, et al: Noninvasive prenatal testing/noninvasive prenatal diagnosis: the position of the National Society of Genetic Counselors. J Genet Counsel 2013;22:291-295

5. Gregg AR, Skotko BG, Benkendorf JL, et al: Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med 2016

6. Jensen TJ, Zwiefelhofer T, Tim RC, et al: High-throughput massively parallel sequencing for fetal aneuploidy detection from maternal plasma. PLOS ONE 2012 Mar;8:1-8

7. Huang X, Zheng J, Chen M, et al: Noninvasive prenatal testing of trisomies 21 and 18 by massively parallel sequencing of maternal plasma DNA in twin pregnancies. Prenatal Diagnosis 2014;34:335-340

Special Instructions Library of PDFs including pertinent information and forms related to the test