Screening test for preeclampsia through assessment of
uteroplacental blood flow and biochemical markers of
oxidative stress and endothelial dysfunction
Mauro Parra, MD,
a,
*
Ramo
´
n Rodrigo, MSc,
b
Pilar Barja,
b
Cleofina Bosco,
b
Virginia Ferna
´
ndez, PhD,
b
Herna
´
n Mun
˜
oz, MD,
a
Emiliano Soto-Chaco
´
n, MD
a
Fetal Medicine Unit, Hospital Clı
´
nico Universidad de Chile,
a
Institute of Biomedical Sciences,
Faculty of Medicine, University of Chile,
b
Santiago, Chile
Received for publication September 23, 2004; revised February 19, 2005; accepted February 22, 2005
KEY WORDS
Preeclampsia
Doppler
Screening
Biochemical markers
Objective: This study was undertaken to evaluate whether screening through a uterine artery
(UtA) Doppler and biochemical markers of oxidative stress and endothelial dysfunction predict
preeclampsia.
Study design: UtA Doppler was performed at 11 to 14 and 22 to 25 weeks on 1447 asymptomatic
pregnant women. Oxidative stress, endothelial dysfunction, and antiangiogenic state were
assessed in women who later developed preeclampsia and normotensive controls.
Results: There was a significantly increased of UtA pulsatility index (PI), plasma levels of soluble
fms-like tyrosine kinase 1 (sFlt1), PAI-1/PAI-2 ratio, and F-2 isoprostane in women who
subsequently developed preeclampsia compared with control pregnancies. Multivariate logistic
regression showed that increased UtA PI performed at 23 weeks was the best predictor for
preeclampsia.
Conclusion: This study demonstrates early changes in markers of impaired placentation,
antiangiogenic state, oxidative stress, and endothelial dysfunction suggesting that these derange-
ments may play a role in the pathogenesis of preeclampsia. Our data point to UtA as the best test to
predict preeclampsia at 23 weeks of gestation.
Ó 2005 Mosby, Inc. All rights reserved.
Preeclampsia (PE) is a systemic disorder of pregnancy
characterized by maternal hypertension, proteinuria,
edema, causing fetal growth restriction, and premature
delivery.
1
Although during the last years there has been a
significant improvement in clarifying the cause of PE,
the underlying pathogenic mechanisms of this disease
remain elusive.
In normal pregnancy, progressive trophoblast inva-
sion transforms the high resistance uteroplacental spiral
arteries into a low-resistance circulation. Histologic
studies have shown that the incomplete process of spiral
artery vascular transformation occurring in pregnancies
affected by PE results in elevated resistance to flow in
Supported by the Fondo Nacional de Ciencia y Tecnologı
´
a
(FONDECYT), grant number 1020080.
* Reprint requests: Mauro Parra, MD, Unidad Medicina Fetal,
Hospital Clı
´
nico Universidad de Chile, Santos Dumont 999, Indepen-
dencia, Santiago, Chile.
E-mail: mcparra@ns.hospital.uchile.cl
0002-9378/$ - see front matter Ó 2005 Mosby, Inc. All rights reserved.
doi:10.1016/j.ajog.2005.02.109
American Journal of Obstetrics and Gynecology (2005) 193, 1486–91
www.ajog.org