About the Test

The MaterniT21 PLUS test, developed and validated by Sequenom CMM, is a laboratory-developed test (LDT) that analyzes circulating cell-free DNA extracted from a maternal blood sample. The test detects the relative amount of 21, 18, 13, X and Y chromosomal material.^1,2

Test Method

Circulating cell-free DNA is purified from the plasma component of anti-coagulated maternal whole blood. The DNA is analyzed for autosomal and Y chromosomal material and converted into a genomic DNA library for the determination of chromosome 21, 18, 13, X and Y representation based on massively parallel DNA sequencing.³

Unique, Proven Circulating Cell-Free Fetal Nucleic Acid (ccff) Technology

• The source of ccff DNA is thought to be from placental cells through the breakdown of fetal cells in circulation^4,5,6,
• Early studies showed ~3-6% of circulating fetal DNA in maternal plasma. Recent studies indicate it may be >10%^7,8
• Analyzes circulating cell-free DNA from maternal blood in women at increased risk for fetal chromosomal aneuploidy
• Sequenom holds an exclusive platform-independent license for fetal nucleic acid detection in serum and plasma, branded under the name SEQureDx^® technology

Clinically Validated, Published Study

The performance characteristics of the MaterniT21 PLUS test have been determined in a large clinical validation study with 4,664 pregnant women at increased risk for fetal chromosomal aneuploidies. This study was independently designed and analyzed by Women and Infants Hospital of Rhode Island (WIHRI), part of the Alpert Medical School of Brown University.^1,2,10

The MaterniT21 PLUS test detects fetal aneuploidies for chromosomes 21, 18, 13 in singletons, twins and higher order multiple pregnancies.^2,9,10 The test also makes a determination for chromosomes X and Y.¹¹ Sex chromosomal aneuploidies are not reported in multiple pregnancies.

A patient with a positive result should be referred for genetic counseling and offered invasive prenatal diagnosis for confirmation of test results.¹² Results from this test do not eliminate the possibility that other chromosomal abnormalities may exist in this pregnancy and a negative result does not ensure an unaffected pregnancy. While results of this testing are highly accurate, not all chromosomal abnormalities may be detected due to placental, maternal or fetal mosaicism, or other causes.

Our Test

This laboratory-developed test was developed and its performance characteristics determined by Sequenom CMM. It has not been cleared or approved by the U.S. Food and Drug Administration (FDA). Although laboratory-developed tests to date have not been subject to U.S. FDA regulation, certification of the laboratory is required under CLIA to ensure the quality and validity of the tests. This laboratory is accredited and certified to perform high complexity clinical laboratory testing.

References

1. Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Deciu C, Grody WW, Nelson SF, Canick JA. DNA Sequencing of Maternal Plasma to Detect Down syndrome: An International Clinical Validation. Genet Med. 2011;13(11):913-920.
2. Palomaki GE, Deciu C, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Grody WW, Nelson SF, Canick JA. DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13, as well as Down syndrome: An international collaborative study. Genet Med. 2012;14(3):296-305.
3. Ehrich M, Deciu C, Zwiefelhofer T, Tynan JA, Cagasan L, Tim R, Lu V, McCullough R, McCarthy E, Nygren AO, Dean J, Tang L, Hutchison D, Lu T, Wang H, Angkachatchai V, Oeth P, Cantor CR, Bombard A, van den Boom D. Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am J Obstet Gynecol. 2011;204(3):205.
4. Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, Wainscoat JS. Presence of fetal DNA in maternal plasma and serum. Lancet. 1997;350(9076):485-487.
5. Finning KM, Martin PG, Soothill PW, Avent ND. Prediction of fetal D status from maternal plasma: introduction of a new noninvasive fetal RHD genotyping service. Transfusion. 2002;42(8):1079-1085.
6. Bianchi DW. Circulating fetal DNA: its origin and diagnostic potential-a review. Placenta. 2004;25 Suppl A:S93-S101.
7. Ding C, Chiu RW, Lau TK, Leung TN, Chan LC, Chan AY, Charoenkwan P, Ng IS, Law HY, Ma ES, Xu X, Wanapirak C, Sanguansermsri T, Liao C, Ai MA, Chui DH, Cantor CR, Lo YM. MS analysis of single-nucleotide differences in circulating nucleic acids: Application to noninvasive prenatal diagnosis. Proc Natl Acad Sci USA. 2004;101(29):10762-10767.
8. Gautier E, Benachi A, Giovazngrandi Y, Ernault P, Olivi M, Gaillon T, Costa JM. Fetal RhD genotyping by maternal serum analysis: a two-year experience. Am J Obstet Gynecol. 2005;192(3):666-669.
9. Canick JA, Kloza EM, Lambert-Messerlian GM, Haddow JE, Ehrich M, van den Boom D, Bombard AT, Deciu C, Palomaki GE. DNA sequencing of maternal plasma to identify Down syndrome and other trisomies in multiple gestations. Prenat Diagn. 2012;32(8):730-734.
10. Mazloom AR, et al. Accuracy of Noninvasive Prenatal Sex Determination using Massively Parallel Sequencing in Samples from a Large Clinical Validation Study. Poster presented at the 2012 Annual American Society of Human Genetics Meeting, November 6-10, 2012; San Francisco, CA.
11. Sequenom Center for Molecular Medicine, submitted for publication, 2013.
12. Committee opinion no. 545: Noninvasive prenatal testing for fetal aneuploidy. Obstet Gynecol. 2012;120(6):1532-1534.