Initial clinical laboratory experience in noninvasive prenatal testing for fetal aneuploidy from maternal plasma DNA samples

Prenat Diagn. 2013 Jun;33(6):569-74. doi: 10.1002/pd.4123.

Abstract

Objective: The aim of this study is to report the experience of noninvasive prenatal DNA testing using massively parallel sequencing in an accredited clinical laboratory.

Methods: Laboratory information was examined for blood samples received for testing between February and November 2012 for chromosome 21 (Chr21), Chr18, and Chr13. Monosomy X (MX) testing was available from July 2012 for cystic hygroma indication. Outcomes were collected from providers on samples with positive results.

Results: There were 5974 samples tested, and results were issued within an average of 5.1 business days. Aneuploidy was detected in 284 (4.8%) samples (155 Chr21, 66 Chr18, 19 Chr13, 40 MX, and four double aneuploidy). Follow-ups are available for 245/284 (86%), and 77/284 (27.1%) are confirmed, including one double-aneuploidy case concordant with cytogenetics from maternal malignancy. Fourteen (0.2%) discordant (putative false-positive) results (one Chr21, six Chr18, three Chr13, three MX, and one Chr21/13) have been identified. Five (0.08%) false-negative cases are reported (two trisomy 21, two trisomy 18, and one MX). In 170 (2.8%) cases, the result for a single chromosome was indefinite.

Conclusions: This report suggests that clinical testing of maternal cell-free DNA for fetal aneuploidy operates within performance parameters established in validation studies. Noninvasive prenatal testing is sensitive to biological contributions from placental and maternal sources.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aneuploidy*
  • DNA / blood*
  • DNA / genetics*
  • Efficiency, Organizational
  • Female
  • Fetus / metabolism
  • Genetic Testing / methods
  • Genetic Testing / statistics & numerical data
  • Humans
  • Laboratories, Hospital / organization & administration
  • Middle Aged
  • Mothers
  • Pregnancy / blood
  • Prenatal Diagnosis / methods*
  • Prenatal Diagnosis / statistics & numerical data
  • Retrospective Studies
  • Young Adult

Substances

  • DNA