Original Paper
Fetal Diagn Ther 2013;33:215–223
DOI: 10.1159/000346806
Maternal Plasma Cell-Free Fetal and Maternal
DNA at 11–13 Weeks’ Gestation: Relation to
Fetal and Maternal Characteristics and
Pregnancy Outcomes
L.C.Y. Poon
a
T. Musci
c
K. Song
c
A. Syngelaki
a
K.H. Nicolaides
a, b
a
Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital, and
b
Department of Fetal Medicine,
University College London Hospital, London, UK;
c
Ariosa Diagnostics, San Jose, Calif., USA
racial origin than in Caucasians, and lower in smokers, but it
was not significantly altered in pregnancies complicated by
PE, SPB or SGA. The fetal cfDNA level was inversely related to
maternal weight and uterine artery pulsatility index, and ma-
ternal cfDNA increased with maternal weight. Conclusions:
The fetal and maternal cfDNA level in maternal plasma is af-
fected by maternal and fetal characteristics, but it is not al-
tered in pregnancy complications.
Copyright © 2013 S. Karger AG, Basel
Introduction
Analysis of cell-free DNA (cfDNA) in maternal blood
can detect more than 99% of pregnancies with trisomy 21
at a false-positive rate of less than 1% [1–9]. Consequent-
ly, this method is far superior to all currently available
approaches to screening for trisomy 21 [10]. A potential
issue with analysis of cfDNA as a universal screening test
in all pregnant women is the failure rate in providing a
result, which primarily depends on the relative propor-
tion of fetal cfDNA to maternal cfDNA in maternal plas-
ma. In trisomic pregnancies the number of molecules de-
rived from the extra fetal chromosome, as a proportion of
Key Words
Cell-free fetal DNA · Cell-free maternal DNA · First-trimester
screening · Preeclampsia · Small for gestational age ·
Preterm birth
Abstract
Objective: To examine the possible relationship between
maternal and fetal characteristics and pregnancy outcomes
on fetal and maternal cell-free (cf) DNA in maternal plasma
at 11–13 weeks’ gestation. Methods: cfDNA was extracted
from maternal plasma of 1,949 singleton pregnancies and
chromosome-selective sequencing was used to determine
the proportion of cfDNA and total cfDNA counts which was
of fetal and maternal origin. Multivariate regression analysis
was used to determine whether specific maternal and fetal
characteristics and pregnancy complications, such as pre-
eclampsia (PE), early spontaneous preterm birth (SPB) and
delivery of small for gestational age (SGA) neonates, were
significant predictors of fetal and maternal cfDNA in mater-
nal plasma. Results: The fetal and maternal cfDNA plasma
concentration increased with serum pregnancy-associated
plasma protein-A and free β-human chorionic gonadotropin
level, was higher in women of Afro-Caribbean and East-Asian
Received: December 26, 2012
Accepted after revision: January 4, 2013
Published online: March 5, 2013
Prof. K.H. Nicolaides
Harris Birthright Research Centre for Fetal Medicine
King’s College Hospital, Denmark Hill
London SE5 9RS (UK)
E-Mail kypros @ fetalmedicine.com
© 2013 S. Karger AG, Basel
1015–3837/13/0334–0215$38.00/0
E-Mail karger@karger.com
www.karger.com/fdt
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