Placenta 33, Supplement A, Trophoblast Research, Vol.

26 (2012) S42eS47

Contents lists available at SciVerse ScienceDirect

Placenta
journal homepage: www.elsevier.com/locate/placenta

Review: Biochemical markers to predict preeclampsia

U.D. Anderson a, M.G. Olsson b, K.H. Kristensen c, B. kerstrm b, S.R. Hansson c, *
a

Department of Obstetrics and Gynecology, Department of Clinical Sciences, Lund University Hospital, Lund University, Tornavgen 10, 22184 Lund, Sweden
Division of Infection Medicine, Department of Clinical Sciences, Lund University, Sweden
c
Department of Obstetrics and gynecology, Department of Clinical Sciences, Malm University Hospital, Lund University, Sweden
b

a r t i c l e i n f o

a b s t r a c t

Article history:
Accepted 23 November 2011

Worldwide the prevalence of preeclampsia (PE) ranges from 3 to 8% of pregnancies. 8.5 million cases are
reported yearly, but this is probably an underestimate due to the lack of proper diagnosis. PE is the most
common cause of fetal and maternal death and yet no specic treatment is available. Reliable
biochemical markers for prediction and diagnosis of PE would have a great impact on maternal health
and several have been suggested. This review describes PE biochemical markers in general and rst
trimester PE biochemical markers specically. The main categories described are angiogenic/antiangiogenic factors, placental proteins, free fetal hemoglobin (HbF), kidney markers, ultrasound and
maternal risk factors. The specic biochemical markers discussed are: PAPP-A, s-Flt-1/PlGF, s-Endoglin,
PP13, cystatin-C, HbF, and a1-microglobulin (A1M). PAPP-A and HbF both show potential as predictive
biochemical markers in the rst trimester with 70% sensitivity at 95% specicity. However, PAPP-A is not
PE-specic and needs to be combined with Doppler ultrasound to obtain the same sensitivity as HbF/
A1M. Soluble Flt -1 and PlGF are promising biochemical markers that together show high sensitivity from
the mid-second trimester. PlGF is somewhat useful from the end of the rst trimester. Screening pregnant women with biochemical markers for PE can reduce unnecessary suffering and health care costs by
early detection of mothers at increased risk for PE, thus avoiding unnecessary hospitalization of pregnant
women with suspect or mild PE and enabling monitoring of the progression of the disease thereby
optimizing time for delivery and hopefully reducing the number of premature births.
2012 Published by IFPA and Elsevier Ltd.

Keywords:
Biochemical markers
Prediction
Preeclampsia
st-1
PlGF
PAPP-A
Fetal hemoglobin
HbF
Alpha-1-microglobulin
A1M
PP13

1. Introduction
Preeclampsia (PE) is one of the most serious pregnancy
complications. The worldwide prevalence of PE ranges from 3 to 8%
of pregnancies, affecting a total of 8.5 million women worldwide.
PE is responsible for about 18% of maternal deaths and up to 40% of
fetal mortality. At this time, PE still lacks a safe and effective
therapy, as well as a reliable, early means of diagnosis or prediction.
PE has been named the "disease of theories" [1] and was
described as a pregnancy-related disease as early as 3000 years
ago by the ancient Egyptians [2]. The disease evolves in two
stages. The rst stage is characterized by an altered formation of
the placenta [3]. During placentation a defective invasion of the
extravillous trophoblast cells into the muscle layers of the spiral
arteries has been shown [4]. This contributes to a reduced uteroplacental blood ow that can result in fetal intrauterine growth
restriction (IUGR), seen in one of four women with PE. A growing

* Corresponding author. Tel.: 46 462223011.

E-mail address: stefan.hansson@med.lu.se (S.R. Hansson).
0143-4004/$ e see front matter 2012 Published by IFPA and Elsevier Ltd.
doi:10.1016/j.placenta.2011.11.021

body of evidence suggests that oxidative stress further aggravates

vascular function in the placenta [5], which in turn [6] gives rise to
insufcient blood perfusion [7], inammation, apoptosis and
structural damage [8e10]. The second stage, the clinical manifestations, i.e. hypertension and proteinuria, appears from 20
weeks of gestation onwards. As the disease progresses, angiospasms in the brain and brain edema may cause severe epileptic
seizures e eclampsia [11].
According to the International Society for the Study of Hypertension in Pregnancy (ISSHP), PE can be dened as de novo hypertension occurring after 20 weeks of pregnancy together with
proteinurea. Hypertension is dened as a systolic blood pressure

140 and/or a diastolic blood pressure
90 mmHg measured at two
occasions with at least 4 h in between. Proteinurea is dened as

300 mg per day [12]. Proteinurea is questionable as a marker for PE
since it lacks predictive value and does not correlate with severity
of the disease.
A severe form of PE is the Hemolysis, Elevated Liver enzymes
and Low Platelets syndrome (the HELLP-syndrome). It is dened by
the laboratory ndings of hemolysis, elevated liver enzymes and
low platelet count [13]. Altogether, the wide range of clinical

U.D. Anderson et al. / Placenta 33, Supplement A, Trophoblast Research, Vol. 26 (2012) S42eS47

manifestations makes PE more syndrome-like than a dened

disease, which complicates the clinical diagnosis [14]. Lately, the
time of onset of the clinical manifestations, early onset PE (<34
weeks of gestation) and late onset PE (>34 weeks of gestation), have
been used to further characterize PE, but the overall classication
still lacks stringency.
In the last decade, methodologies such as genomics, proteomics
and metabolomics have been made more widely available for
clinical research. In search of the etiology of PE, several new
pathways and factors have been described using these techniques.
Many of the described etiological factors are measurable in the
maternal blood and have therefore been evaluated as biochemical
markers for prediction and diagnosis of PE. These include serum/
plasma markers for renal dysfunction, endothelial dysfunction,
metabolic status, oxidative stress, placenta-derived factors, hemolysis and inammatory markers.
Several maternal clinical characteristics have been identied as
risk factors for developing PE. The most important of these are
ethnicity, age, parity, multiple pregnancy and a history of PE in
earlier pregnancies. In addition, some systemic disorders also
increase the risk: obesity, diabetes mellitus, essential hypertension, renal disease, antiphospholipid syndrome and certain autoimmune diseases [15]. However, none of these alone or in
combination predict PE sufciently, as they are reported to have
a combined prediction rate of about 30%, early onset PE better
than late onset PE [16].
Few biochemical markers have been proven specic and sensitive as single markers to predict and/or diagnose PE. Algorithms
also include clinical measurements such as Doppler ultrasound and
clinical risk factors, to further enhance the prediction rate at a low
false positive rate. In this review we describe the most promising
individual biochemical markers suggested for both prediction and
diagnosis of PE. The biochemical markers are presented in the order
they are shown to appear in pregnancy, i.e. rst, second or third
trimester.

S43

2. Predictive biochemical markers

PAPP-A, PlGF and the combination HbF/A1M all show potential
as predictive biochemical markers in the rst trimester (Table 1).
2.1. Pregnancy-associated protein A (PAPP-A)
PAPP-A is a glycoprotein synthesized in the placenta and the
study of it as a biochemical marker in pregnancy has been pursued
for almost 30 years [17]. The maternal plasma concentration
increases throughout pregnancy. PAPP-A has been used in combination with b-human chorionic gonadotropin (b-hCG) and nucal
translucency thickness, to screen for trisomy 21, 13 and 18 at 11 0
to 13 6 weeks of gestation [18]. In fetuses with normal chromosomes, decreased levels of PAPP-A in the rst trimester have
been associated with increased risk for PE, IUGR, fetuses small for
gestational age (SGA) and preterm delivery [19e22].
PAPP-A has been evaluated as a predictive and diagnostic
biochemical marker for PE, but the screening performance, when
used as a single biochemical marker, is only about 10e20 %
[23e25]. Combined with Doppler ultrasound, PAPP-A is a powerful
predictive biochemical marker of PE with prediction rates of 70% at
false positive rates of 5%. At term, plasma PAPP-A concentrations
have been shown to increase in pregnancies complicated by PE and
HELLP, but its concentration is still not predictive for the severity of
the disease [26].
2.2. Fetal hemoglobin and a1-microglobulin
Recent reports suggest that free, extracellular fetal hemoglobin
(HbF) is involved in the pathogenesis of PE. Furthermore the hemeand radical scavenger a1-microglobulin (A1M) is involved in the
physiological defence against HbF. Their concentrations in maternal
serum or plasma can be used as early predictive biochemical
markers. Increased mRNA levels of HbF in the placental tissue and

Table 1
Biochemical prediction markers of preeclampsia. Shown with function, gestational age at sampling and prediction rate/false positive rate. Prediction rates are given for all kinds
of preeclampsia.
Biochemical marker

Function of protein

Gestational age
at prediction

Prediction rate/false positives

Free fetal hemoglobin (HbF)

and alpha-1-microglobulin
(A1M)
Pregnancy-associated Protein A
(PAPP-A)

Oxygen transportation protein in the

fetus and A1M is an antioxidant and
a heme scavenger
In fetuses with normal chromosomes
in probably inuences placental
development.

10 0e16 0

69%/5% [8]
Optimal 90%/23% [8]

11 0e13 6

Placental Protein 13 (PP13)

A member of the Galectin family.

Function(s) are unclear e but it
probably induces apoptosis in
some immune cells.

11 0e13 6

Soluble Endoglin

Anti-angiogenetic protein

11 0e13 6

Metabolomics

Metabolites measured in maternal

blood as a nal down stream product
of gene expression.
PlGF and sFlt-1 regulate angiogenesis
of the placenta.

14 0e16 0

9.6e20.1%/5% [20, 24]

20.5e50%/10% [20, 24]
In combination with Doppler
ultrasound - 25e64.4%/5%
[20, 24, 38]
37.5%a/5% [38]
52.1ae80b%/10% [38, 39]
43%/20% [40]
In combination with Doppler
ultrasound e 66.7%a/5% [38] or
71.4e77.1%/10% [38, 39]
30%/5% [51]
In combination with Doppler
ultrasound e 66.7/5% [50]
77%/10% [55]

Angiogenesisfactors
(SFlt-1/PlGF)
PlGF alone

a
b

Combined with maternal risk factors.

Early onset PE only, and combined with maternal risk factors.

Second trimester:
24 0 and throughout
pregnancy.
11 0e13 6

82%/5% [53]
88.5%/10% [53]
88.5%/11.5% [54]
53.5%/5% [16]
65%/10% [16]

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U.D. Anderson et al. / Placenta 33, Supplement A, Trophoblast Research, Vol. 26 (2012) S42eS47

free HbF protein in the placental vascular lumen were described in

women with PE [27]. Hemoglobin is a highly reactive molecule that
is capable of damaging and disrupting cell membranes [28], and
binds and inactivates nitric oxide (NO) with vasoconstriction as
a consequence [29]. Its metabolites, heme and iron, damage lipids,
protein and DNA through direct oxidation and/or generation of
reactive oxygen species (ROS). Heme is also a pro-inammatory
molecule that activates neutrophils [30]. Several Hb- and hemedetoxication systems have been described in humans. Recently,
the plasma and tissue protein A1M was shown to bind and degrade
heme [31], have radical-scavenger properties [32], and protect cells
and tissues against extracellular Hb, heme and ROS [33,34]. A1Mexpression in liver and placental cells has been shown to be upregulated by Hb, heme and ROS [33,35]. A pathogenic role of Hb
and protective role of A1M in PE is supported by ex vivo placenta
perfusion experiments [9].
Studies evaluating maternal serum/plasma concentrations of
HbF and A1M, as predictive and diagnostic markers for PE, have
shown promising results [8,33]. In a cohort of 96 patients (60
subsequently developed PE) the serum concentrations of HbF and
A1M were signicantly increased at 10e16 weeks gestation in
women who subsequently developed PE. The AUC for the ROCcurve was 0.89 for the two biochemical markers in combination.
At a false positive rate of 5% the prediction rate was 69%. Optimal
prediction rate was 90% for a false positive rate of 23% [8]. The
plasma concentrations of HbF and adult hemoglobin (HbA) were
also signicantly correlated to maternal blood pressure in patients
with established PE [33]. These markers still need to be validated in
larger cohorts.
2.3. Placental protein 13 (PP13)
PP13 is a member of the galectin family and is produced by the
placental trophoblast cells [36,37]. The function(s) of PP13 is still
not clearly understood, but it is involved in normal placentation
[36]. In normal pregnancies, serum levels of PP13 slowly rise with
gestational age. Several studies have shown lowered serum levels
in the rst trimester in pregnancies that subsequently developed
PE. As a rst trimester screening marker for PE, PP13 shows
different prediction rates in different studies. In two different
cohort studies, PP13 levels were determined at 11 0 to 13 6
weeks of gestation [38,39]. Both studies showed signicantly lower
rst trimester levels of PP13 in women who later developed PE. At
false positive rates of 5% and 10% they found detection rates of 37.5%
and 69% respectively, using PP13 as a single biochemical marker.
When combining serum screening with Doppler ultrasound pulsatility index (PI), the prediction rate increased to 71% at a false
positive rate of 10% [39].
Romero et al. [40] studied a cohort of 300 patients 50 of which
developed PE. At a false positive rate of 20% the detection rate was
36% for all types of PE. For early onset PE it was 100% (n 6) and for
preterm PE 85% (n 44). Preterm was dened as onset before
37 0 weeks. The prediction rate for severe PE at term was 24%
(n 21). Based on these ndings, PP13 was concluded to be
a reasonable biochemical marker for early onset and preterm PE but
a weak marker for PE at term [40].
Nicolaides et al. [41] studied PP13 as a biochemical marker for
early onset PE at 11 0 to 13 6 weeks of gestation. At a false
positive rate of 10%, PP13 showed a prediction rate of 80% as a single
biochemical marker. In combination with Doppler ultrasound PI,
the prediction rate increased to 90% [41].
PP13 has also been used in combination with PAPP-A. In a cohort
of 499 patients (47 PE cases) Stamatopoulou et al. [42] studied PP13
and PAPP-A at 11 0 to 13 6 weeks of gestation in hypertensive
pregnancies and pregnancies complicated by SGA. They found that

PAPP-A was signicantly lower in SGA and in hypertensive disorders but interestingly, the levels of PP13 did not differ between the
cases and the controls [42].
2.4. Soluble fms-like tyrosine kinase 1(sFlt-1) and soluble endoglin
(sEng)
Two angiogenesis-related factors are particularly well studied:
soluble fms-like tyrosine kinase (sFlt-1), a soluble VEGF receptor,
and soluble endoglin (s-Eng), a co-receptor for TGF-beta. Both are
elevated in maternal plasma in patients with PE compared to
normal pregnancies [43e46]. Elevated levels of sFlt-1 occur before
the clinical symptoms. The levels correlate with the time of onset of
clinically manifest PE and partly with disease severity. Early-onset
PE exhibits higher levels of sFlt-1 [43,44,47,48]. Moreover, in animal
experiments, proteinuria and hypertension, as well as a HELLP-like
syndrome, were induced by infusion of high levels of sFlt and
endoglin [49].
As a rst trimester screening marker, s-Eng shows conicting
results [50]. Used in combination with Doppler ultrasound (PI) and
PlGF, the prediction rate for early onset PE was 77.8% at a false
positive rate of 5%. AUC of the ROC curve was 0.95 [51].
2.5. Placental growth factor (PlGF) and sFlt-1
The ratio of the PlGF/sFlt-1 is well described and a promising set
of biochemical markers for prediction of PE [52]. Automated fast
analysis methods have been developed for these proteins [53], but
their role as rst trimester markers is not clear [52].
Several studies have shown the predictive power of PlGF/sFlt-1
ratio from the second trimester. The prediction rate is about 89%
[54]. In a recent multicenter study by Verlohren et al. [53],
including 351 patients (71 with PE), the sFlt-1/PlGF ratio was
measured longitudinally throughout pregnancy. The AUC of the
ROC-curve for detecting PE was 0.95. At a false positive rate of 5%
the detection rate was 82% for all PE. For early onset PE, at a false
positive rate of 3%, the detection rate was 89% [53]. Hence, the sFlt1/PlGF ratio has no predictive value in the rst trimester. As a single
biochemical marker, PlGF has been shown to predict 53.5% of early
onset PE at a false positive rate of 5% and 65% at a false positive rate
of 10% [16] in late rst trimester.
2.6. Metabolomics
Metabolic proling is a powerful strategy to investigate the
metabolites that a specic cellular event leaves behind. Metabolic
proling can be used to reveal the pathophysiological mechanisms
in a disease such as PE [55]. Recently, in a study of 60 patients who
subsequently developed PE and 60 normal pregnancies, 45
metabolites were shown to be signicantly altered in the rst
trimester in pregnancies that later developed PE. A predictive
model, based on 14 metabolites showed AUC of the ROC-curve to be
0.94. For early and late onset PE, the prediction rate was between 73
and 77% at a 10% false positive rate [55]. The ndings were validated
in a cohort of 39 patients with subsequent PE matched with 40
normal pregnancies. Interestingly, 3 out of the 40 up-regulated
metabolites were shown to be hemoglobin metabolites.
2.7. Cystatin C
Cystatin C is a protease inhibitor widely used by clinicians as
a sensitive marker for renal function and for estimation of
glomerular ltration rate. The maternal plasma level of cystatin C is
increased in women with PE and studies have demonstrated that
the level of cystatin C is a reliable diagnostic marker for PE [56,57].

U.D. Anderson et al. / Placenta 33, Supplement A, Trophoblast Research, Vol. 26 (2012) S42eS47

Increased levels of cystatin C are suggested to be caused by either

impaired renal function and/or by increased placental synthesis
[58]. Cystatin C has recently been suggested as a predictive rst
trimester marker for PE [59]. However, given the low screening
performance of the study, cystatin C is probably not clinically useful
as a single marker but could be useful in combination with other
predictive markers [60].
2.8. Other biochemical markers
As genomics, proteomics and metabolomics are being developed and made more available, the number of potential biochemical markers will increase. Ideally, the biochemical markers will
give us new hints as to the pathogenesis behind PE. These new
techniques have revealed many of the above mentioned biochemical markers, and worth mentioning are free mRNAs [61] and
miRNAs [62] in maternal blood. Both types of RNAs are expressed in
the placenta and can be found in the maternal circulation. Further
investigation is needed but proling of these RNAs might show
potential in predicting pregnancy outcomes.

S45

and 60.9% for late onset PE [16] (intermediate onset PE was dened
as PE that led to delivery between 34 0 and 36 6 weeks of
gestation). Wortelboer et al. [63] developed a model based on the
rst trimester biochemical markers, PAPP-A, beta-hCG, PlGF,
desintegrin and ADAM metallopeptidase domain 12 (ADAM12).
Their prediction of all PE was only 44% at a 5% false positive rate
[63]. Another rst trimester model based on maternal characteristics, PI and the biochemical markers PAPP-A, inhibin-A, PP13,
ADAM12, free beta-hCG and PlGF was developed by Audibert et al.
[64]. In a large cohort (n 893) the model showed a 100%
prediction rate for early onset PE at a false positive rate of 10% [64].
It is worth noting that PP13 and ADAM12 levels did not improve the
prediction rates. In a very recent study by Odibo et al. [65] maternal
characteristics were combined with serum PP13, PAPP-A and PI in
the rst trimester. In a cohort of 450 patients, the prediction rate
was 68% at a false positive rate of 5%. Interestingly, PI measurements did not increase the prediction rate in this study [65].
3. Discussion
The ideal biochemical marker for PE should exhibit the
following characteristics:

2.9. New algorithms

The lack of a specic and sensitive biochemical marker has led to
the development of mathematical models that combine several
factors in order to predict PE (Table 2). Akolekar et al. [16] combined
maternal characteristics, PI and mean arterial pressure (MAP) with
serum levels of PAPP-A, PlGF, PP13, inhibin-A, activin-A, sEng,
pentraxin-3 and p-selectin in a large study (n 33,602) at 11 0 to
13 6 weeks of gestation. The prediction rates, at a false positive
rate of 5%, were 91% for early onset, 79.4% for intermediate onset
Table 2
Suggested algorithms of predictional biochemical/biophysical markers of PE. Shown
with gestational age at prediction, prediction rates and false positives. Prediction
rates are for all PE e unless else is noted.
Combination of
biochemical/biophysical
markers

Gestational age
at prediction

Prediction rate/false
positives

Model 1 [16]
Doppler ultrasound PI
Mean arterial blood
pressure
PAPP-A
PlGF
PP13
Inhibin-A
Activin-A
sEng
Pentraxin-3
p-Selectin

110e136

91% for early onset PE

79% for intermediate
onset PE
61% for late onset PE/5%

Model 2 [63]
PAPP-A
Beta-hCG
PlGF
Desintegrin
ADAM12

First trimester

44%/5%

Model 3 [64]
Doppler Ultrasound L-PI
PAPP-A
Inhibin-A
PlGF

110e136

40%/10%
100%/10% for early
onset PE

Model 4 [65]
PP13
PAPP-A
Doppler ultrasound

110e140

68%/5%

1) Play a central role in the pathogenesis and be specic for the

condition.
2) Appear early or before the clinical manifestations. Placental
factors that can be detected early in pregnancy are likely to be
good biochemical marker candidates for PE prediction.
However, placental disorders can cause IUGR without PE and
vice versa, which makes the clinical evaluation of new markers
particularly hard.
3) Be easy and cheap to measure in maternal blood or urine. Few
of the described factors are easy to measure; most of them
require advanced laboratory systems.
4) Show a high sensitivity and specicity. A small number of the
described biochemical markers fulll this requirement and
strategies to use them in combination with other markers and/
or, with PI measurements and other clinical parameters are
being investigated.
5) Correlate with the severity of the condition. As the disease
progresses, several organ systems are affected, which causes
the number of factors to increase throughout pregnancy. A
good candidate marker ought to appear early in pregnancy and
continue to rise as the disease progresses.
6) Be non-detected or expressed at very low levels in normal
pregnancies. Again, a placental factor is favored since the
clinical symptoms disappear after removal of the placenta.
Screening pregnant women with an effective diagnostic marker
for PE  IUGR could reduce unnecessary suffering and major health
care costs [66]. PE is still a dominant problem in the Third World,
where it is often rst diagnosed when the women present with
eclamptic seizures. Basic equipment for blood pressure monitoring
is often lacking, which requires clinicians to make careful clinical
observations and basic examinations. Fetal monitoring with
Doppler ultrasound and ECG is rarely available. Therefore, algorithms that summarize maternal risk factors are valuable and it is
most important to develop them further. In order for a PE
biochemical marker to be useful in the Third World, the need for
simplicity cannot be emphasized enough. Furthermore, the
biochemical marker must be detectable before the disease progresses into a dangerous stage, so that remote health care centres can
refer their pregnant women to larger hospitals in timely manner.
In the Western world, the trend goes towards general and early
screening for defects and diseases. Screening for Downss

S46

U.D. Anderson et al. / Placenta 33, Supplement A, Trophoblast Research, Vol. 26 (2012) S42eS47

syndrome in the rst trimester is a good example where a combination of ultrasound scanning and biochemical markers are used.
This could be a suitable time also to screen for PE [67]. It is generally
accepted, and a part of the WHO criteria, that when setting up
a screening model for diseases like PE, the accepted level of false
positives is set to 5%. However, as described above, published
results sometimes describe prediction rates at false positive rates of
10%, 20% or higher. Potential rst trimester biochemical markers
are PAPP-A [18], HbF and A1M [8]. Both HbF and A1M play a role in
the pathophysiology of PE [9,27,33]. The biochemical markers
appear as early as 10 weeks of gestation [8]. Furthermore, they can
be measured with basic ELISA techniques and show a high
prediction rate at a low false positive level. Maternal plasma
concentrations of free HbF have also been shown to correlate well
with severity, i.e. blood pressure, in term PE pregnancies [33].
Angiogenic and anti-angiogenic factors are also very promising
biochemical markers. Although the combination sFlt-1/PlGF might
not be useful in the rst trimester, they are denitely well evaluated
in the second trimester. Alterations of sFlt-1 and PlGF levels occur
about 6 weeks before the onset of clinical symptoms and correlate
with the severity of the disease. PlGF could be a promising
biochemical marker even in the rst trimester particularly if
combined with HbF and A1M.
PP13 has shown potential as a biochemical marker of early onset
PE. Especially if combined with Doppler ultrasound uterine artery
PI [41]. However, as a general screening marker for all types of PE,
the data is conicting and needs further investigation.
Metabolomics is a promising technique to reveal early pathophysiological mechanisms. The predictive model, based on 14
metabolites measured at 1416 weeks of gestation, is interesting as it
meets the rst criterion of a good predictive biochemical marker
and appears before onset of the maternal symptoms [55]. The
model has a high sensitivity, and might be used as a screening
model. However, due to the complex requirements regarding
sample collection and analysis, the method may be difcult to
implement into clinical praxis, particularly in the Third World.
New factors should not be viewed solely as competing
biochemical markers for prediction and diagnosis of PE. Instead,
each new factor ought to be welcomed as a new important puzzlepiece that contributes to illuminating the etiology of PE. In the end
these advances will hopefully lead to better prophylactic treatments reducing maternal and fetal morbidity.
Conict of interest
The authors Stefan R. Hansson, Magnus G. Olsson and Bo kerstrm hold patents related to prediction, diagnosis and treatment
of preeclampsia.
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