Preeclampsia's threat calls for testing

May 1, 2010

Preeclampsia is a
major cause of maternal and perinatal mortality and morbidity worldwide.
This multisystemic disorder affects approximately 5% to 10% of pregnant
women toward the end of the second trimester of gestation. Clinically,
this disease is characterized by hypertension and proteinuria, an excess
of serum proteins in the urine. This clinical condition is a risk for
mother and child, and can make it necessary to induce premature birth.

Preeclampsia can also affect important growth factors causing
malnutrition of the placenta and fetus. Besides adequate and proper
prenatal care, the delivery of the fetus is the only effective
treatment. The decision between delivery and expectant management
depends on gestational age, fetal well-being, and severity of maternal
condition at the time of assessment. Although the pathophysiology of
preeclampsia is still unknown, the placenta is considered to play a key
role in this disease.

The purpose of a screening test for preeclampsia must be the detection
of a high-risk group as early as possible in pregnancy in order to offer
a prophylactic treatment to women at high risk. The only prophylactic
regimen which may lead to a reduction of preeclampsia is low-dose
aspirin. It should start before the complete invasion of the trophoblast
from the 12th to 16th week of pregnancy. The availability of a test to
predict preeclampsia as early as at the end of the first trimester of
gestation would allow a preventive treatment and, thus, provide a
powerful tool in reducing preeclampsia-induced risks for the mother and
fetus.

Several genetic markers on the placenta are currently discussed as
indications as to the likelihood of a woman developing pregnancy
complications such as preeclampsia or fetal growth restriction. Although
they were once thought to be static after the first trimester,
researchers have found that many of these markers change over the course
of the pregnancy, which might make it possible to identify windows of
opportunity to detect and respond to risks. Among these marker proteins,
placental growth factor (PLGF), a member of the vascular endothelial
cell growth factor (VEGF) family, is produced chiefly by the placenta
and is a potent angiogenic factor. Angiogenesis and vascular
transformation are important processes in the normal development of the
placenta; abnormal angiogenesis and vascular transformation are
considered to be two of the main reasons for preeclamptic pregnancies
and intrauterine growth retardation.

Studies conducted in 2007 first showed that the PLGF concentration in
normal pregnancies constantly increased during pregnancy, peaked at 28
to 32 weeks, and consistently declined thereafter. The preeclamptic
pregnancy — especially the early onset forms — showed a significantly
lower serum concentration without a peak in the second trimester.
Consequently, low concentrations of PLGF indicated an increased risk for
preeclampsia as early as at the 15th week of pregnancy.

In addition, a combination of measurements of angiogenic factors like
PLGF and abnormal uterine artery Doppler velocimetry in the middle of
the second trimester may be useful in future screening for early
prediction of pregnancy complications. Further studies need to be
carried out to answer the question as to whether the measurement of PLGF
alone or in combination with other factors in the first trimester or at
the beginning of the second trimester may define a group with a high
risk for preeclampsia, which then may benefit from low-dosage aspirin
therapy.

There is research underway concerning testing for preeclampsia.
Currently, several marker proteins are under investigation, potentially
allowing for even earlier testing of preeclampsia in pregnant women.

Matthias Herkert, PhD, is the senior scientist in the
R&D department of DRG Instruments GmbH in Marburg, Germany, a
wholly-owned subsidiary of DRG International.
He is responsible for development of new ELISA kits, and for training
DRG employees and distributors. He also oversees collaboration with
project partners, including university hospitals and research groups.

Published: May, 2010