Natera, San Carlos, Calif, a genetic testing and cell-free DNA analysis company, has announced  results from a new study demonstrating that fetal fraction, as measured by the company’s Panorama noninvasive prenatal test (NIPT), can be used as an independent biomarker to screen for certain chromosomal abnormalities and adverse pregnancy outcomes. Fetal fraction is the proportion of fetal DNA in the mother’s blood, and it is known to increase with gestational age and to decrease with greater maternal weight.


Kimberly Martin, MD.

A recent review published in the New England Journal of Medicine highlighted the increased risk of false-negative results from NIPT tests that fail to measure fetal fraction.1 Other studies have shown a higher rate of certain chromosomal abnormalities in pregnancies with low fetal fraction.2.3

In the new clinical study, Natera statisticians leveraged data from a subset of more than one million Panorama tests to devise an algorithm that identifies cases where the fetal fraction is unexpectedly low given the patient’s weight and gestational age.4 This proprietary algorithm computes a fetal fraction-based risk (FFBR) score for the pregnancy.

The study evaluated outcomes from 1,148 pregnancies with low fetal fraction.4 The results showed that the new FFBR algorithm successfully identified a subgroup of high-risk cases, of which 21.8% had a chromosomal abnormality or adverse outcome. Those cases represented the vast majority of all abnormalities in the cohort, most of which would typically have been missed by conventional NIPTs. Cases in the study not flagged by the FFBR algorithm had no evidence of increased risk.

“Consistent with the joint ACOG and SMFM and ACMG guidelines, Panorama was the first NIPT to measure and report fetal fraction,” says Kimberly Martin, MD, a study coauthor and senior director and head of women’s reproductive health at Natera.5,6 “Now we can use fetal fraction as an independent biomarker to overcome some of the limitations of standard NIPT algorithms, identifying high-risk pregnancies at low fetal fraction.”


Matthew Rabinowitz, PhD, Natera.

Panorama reveals a baby’s risk for severe genetic disorders as early as 9 weeks into pregnancy. The test uses a unique single nucleotide polymorphism (SNP)-based technology to analyze fetal and placental DNA obtained through a blood draw from the mother. It is the only test that differentiates between maternal and fetal DNA in the relevant chromosomes of interest. The test also screens twin pregnancies for the zygosity and the gender of each baby, and identifies risk for many genetic conditions in twin pregnancies. Panorama is one of several genetic screening tests designed to help families on the path to parenthood.

“These developments are the first fruits of an initiative to learn from our vast cohort of patients, further extending Natera’s leadership position by enhancing the information we can deliver,” says Matthew Rabinowitz, PhD, Natera’s CEO. “We look forward to exploring the power of this biomarker to detect other adverse outcomes in SMART, our prospective 20,000 patient study.”

The Panorama NIPT was developed by Natera, a laboratory certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The test has not been cleared or approved by the FDA. Although FDA does not currently clear or approve laboratory-developed tests in the United States, certification of the laboratory is required under CLIA to ensure the quality and validity of the tests.

To learn more, visit Natera.


  1. Bianchi DW, Chiu RWK. Sequencing of circulating cell-free DNA during pregnancy. N Engl J Med. 2018;379(5):464–473; doi: 10.1056/nejmra1705345.
  1. Pergament E, Cuckle H, Zimmermann B, et al. Single-nucleotide polymorphism-based noninvasive prenatal screening in a high-risk and low-risk cohort. Obstet Gynecol. 2014;124(2 Pt 1):210–218; doi: 10.1097/aog.0000000000000363.
  1. Norton ME, Jacobsson B, Swamy GK, et al. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med. 2015;372(17):1589–1597; doi: 10.1056/nejmoa1407349.
  1. McKanna T, Ryan A, Krinshpun S, et al. Fetal fraction-based risk algorithm for noninvasive prenatal testing: screening for trisomy 13, 18, and triploidy in women with low cell-free fetal DNA. Ultrasound Obstet Gynecol. Epub ahead of print, July 16, 2018; doi: 10.1002/uog.19176.
  1. Committee opinion no. 640: cell-free DNA screening for fetal aneuploidy. Obstet Gynecol. 2015;126(3):e31-e37; doi: 10.1097/aog.0000000000001051.
  1. 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;18(10):1056–1065; doi: 10.1038/gim.2016.97.