Noninvasive prenatal testing using a novel analysis pipeline to screen for all autosomal fetal aneuploidies improves pregnancy management

Eur J Hum Genet. 2015 Oct;23(10):1286-93. doi: 10.1038/ejhg.2014.282. Epub 2015 Jan 14.


Noninvasive prenatal testing by massive parallel sequencing of maternal plasma DNA has rapidly been adopted as a mainstream method for detection of fetal trisomy 21, 18 and 13. Despite the relative high accuracy of current NIPT testing, a substantial number of false-positive and false-negative test results remain. Here, we present an analysis pipeline, which addresses some of the technical as well as the biologically derived causes of error. Most importantly, it differentiates high z-scores due to fetal trisomies from those due to local maternal CNVs causing false positives. This pipeline was retrospectively validated for trisomy 18 and 21 detection on 296 samples demonstrating a sensitivity and specificity of 100%, and applied prospectively to 1350 pregnant women in the clinical diagnostic setting with a result reported in 99.9% of cases. In addition, values indicative for trisomy were observed two times for chromosome 7 and once each for chromosomes 15 and 16, and once for a segmental trisomy 18. Two of the trisomies were confirmed to be mosaic, one of which contained a uniparental disomy cell line. As placental trisomies pose a risk for low-grade fetal mosaicism as well as uniparental disomy, genome-wide noninvasive aneuploidy detection is improving prenatal management.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy
  • Chromosome Aberrations
  • Chromosome Disorders / genetics*
  • Chromosomes, Human / genetics*
  • Chromosomes, Human, Pair 18 / genetics
  • Down Syndrome / genetics
  • Female
  • Fetus / pathology
  • Genetic Testing / methods*
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Placenta / pathology
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Retrospective Studies
  • Trisomy / genetics
  • Trisomy 18 Syndrome