Noninvasive prenatal diagnosis of common fetal chromosomal aneuploidies by maternal plasma DNA sequencing

J Matern Fetal Neonatal Med. 2012 Aug;25(8):1370-4. doi: 10.3109/14767058.2011.635730. Epub 2012 Feb 24.


Objective: To develop a new bioinformatic method in the noninvasive prenatal identification of common fetal aneuploidies using massively parallel sequencing on maternal plasma.

Methods: Massively parallel sequencing was performed on plasma DNA samples from 108 pregnant women (median gestation: 12(+5) week) immediately before chorionic villus sampling (CVS) or amniocentesis. Data were analysed using a novel z-score method with internal reference chromosome. The diagnostic accuracies of the fetal karyotyping status were compared against two previously reported z-score methods--one without adjustment and the other with GC correction.

Results: A total of 32 cases with fetal aneuploidy were confirmed by conventional karyotyping, including 11 cases of Trisomy 21, 10 cases of Trisomy 18, 2 cases of Trisomy 13, 8 cases of Turner syndrome (45, XO) and one case of Klinefelter syndrome (47, XXY). Using the z-score method without reference adjustment, the detection rate for Trisomy 21, Trisomy 18, Trisomy 13, Turner syndrome, and Klinefelter's syndrome is 100%, 40%, 0%, 88% and 0% respectively. Using the z-score method with GC correction, the detection rate increased to 100% for Trisomy 21, 90% for Trisomy 18, 100% for Trisomy 13. By using the z-score method with internal reference, the detection rate increased to 100% for all aneuploidies. The false positive rate was 0% for all three methods.

Conclusion: This massively parallel sequencing-based approach, combined with the improved z-score test methodology, enables the prenatal diagnosis of most common aneuploidies with a high degree of accuracy, even in the first trimester of pregnancy.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Adult
  • Amniocentesis
  • Aneuploidy*
  • Blood Chemical Analysis / methods
  • Chorionic Villi Sampling
  • Female
  • Fetal Diseases / diagnosis*
  • Fetal Diseases / genetics
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Karyotyping
  • Mothers
  • Pregnancy / blood*
  • Pregnancy / genetics
  • Pregnancy Trimester, First / blood
  • Pregnancy Trimester, First / genetics
  • Prenatal Diagnosis / methods*
  • Sequence Analysis, DNA* / methods