Vascular Health and Risk Management

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Pre-eclampsia: pathophysiology, diagnosis,

and management
This article was published in the following Dove Press journal:
Vascular Health and Risk Management
18 July 2011
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Jennifer Uzan 1
Marie Carbonnel 1
Olivier Piconne 1,3
Roland Asmar 2
Jean-Marc Ayoubi 1
1
Department of Gynecology and
Obstetrics, Hpital Foch, Suresnes,
France; 2Foundation Medical Research
Institutes, Geneva, Switzerland;
3
Department of Gynecology and
Obstetrics, Hpital Antoine Bclre,
Clamart, France

Abstract: The incidence of pre-eclampsia ranges from 3% to 7% for nulliparas and 1%

to 3% for multiparas. Pre-eclampsia is a major cause of maternal mortality and morbidity,
preterm birth, perinatal death, and intrauterine growth restriction. Unfortunately, the
pathophysiology of this multisystem disorder, characterized by abnormal vascular response
to placentation, is still unclear. Despite great polymorphism of the disease, the criteria for
pre-eclampsia have not changed over the past decade (systolic blood pressure.140mmHg
or diastolic blood pressure $90mmHg and 24-hour proteinuria $0.3g). Clinical features
and laboratory abnormalities define and determine the severity of pre-eclampsia. Delivery is
the only curative treatment for pre-eclampsia. Multidisciplinary management, involving an
obstetrician, anesthetist, and pediatrician, is carried out with consideration of the maternal
risks due to continued pregnancy and the fetal risks associated with induced preterm delivery.
Screening women at high risk and preventing recurrences are key issues in the management
of pre-eclampsia.
Keywords: pre-eclampsia, epidemiology, pathophysiology, therapeutic management

Introduction
The criteria that define pre-eclampsia have not changed over the past decade.1,2 These
are: onset at.20 weeks gestational age of 24-hour proteinuria $30mg/day or, if
not available, a protein concentration $30mg ($1+ on dipstick) in a minimum of
two random urine samples collected at least 46hours but no more than 7days apart,
a systolic blood pressure .140 mmHg or diastolic blood pressure $90 mmHg as
measured twice, using an appropriate cuff, 46hours and less than 7days apart, and
disappearance of all these abnormalities before the end of the 6th week postpartum.
Nonetheless, some presentations of pregnancy-related hypertension combined with
clinical or laboratory abnormalities or intrauterine growth restriction should also be
considered as potential pre-eclampsia.1

Epidemiology
Correspondence: Jean-Marc Ayoubi
Service de Gyncologie et Obsttrique,
Hpital Foch, 92151 Suresnes
Cedex, France
Tel +331 4625 2228
Fax +331 4625 2759
Email [email protected]

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http://dx.doi.org/10.2147/VHRM.S20181

Pre-eclampsia is a multisystem disorder that complicates 3%8% of pregnancies

in Western countries and constitutes a major source of morbidity and mortality
worldwide.3,4 Overall, 10%15% of maternal deaths are directly associated with preeclampsia and eclampsia.4 Some epidemiological findings support the hypothesis of a
genetic and immunological etiology. The risk of pre-eclampsia is 2-fold to 5-fold higher
in pregnant women with a maternal history of this disorder. Depending on ethnicity, the
incidence of pre-eclampsia ranges from 3% to 7% in healthy nulliparas and 1% to 3%

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2011 Uzan etal, publisher and licensee Dove Medical Press Ltd. This is an Open Access article
which permits unrestricted noncommercial use, provided the original work is properly cited.

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in multiparas. Moreover, nulliparity and a new partner have

been shown to be important risk factors (Table 1).5
Other risk factors have been identified, including a
medical history of chronic hypertension, kidney disease,
diabetes, obesity, birthplace in Africa, age $35 years, and
pregnancy characteristics, such as twin or molar pregnancy,
previous pre-eclampsia, or fetal congenital abnormality.6,7
High altitude has also been shown to increase the incidence
of pre-eclampsia, and is attributed to greater placental
hypoxia, smaller uterine artery diameter, and lower uterine
artery blood flow.8
Pre-eclampsia may be life-threatening for both mother
and child, increasing both fetal and maternal morbidity and
mortality.5 In the mother, pre-eclampsia may cause premature
cardiovascular disease, such as chronic hypertension, ischemic
heart disease, and stroke, later in life,9 while children born
after pre-eclamptic pregnancies and who are relatively small at
birth, have an increased risk of stroke, coronary heart disease,
and metabolic syndrome in adult life.1012
The sole curative treatment being delivery, management
must continuously balance the riskbenefit ratio of induced
preterm delivery and maternalfetal complications. Screening
women at high risk and preventing recurrences are also key
issues in the management of pre-eclampsia.

Pathophysiology
During normal pregnancy, the villous cytotrophoblast
invades into the inner third of the myometrium, and spiral
arteries lose their endothelium and most of their muscle
fibers. These structural modifications are associated with
functional alterations, such that spiral arteries become lowresistance vessels, and thus less sensitive, or even insensitive,
to vasoconstrictive substances.
Pre-eclampsia has a complex pathophysiology, the primary cause being abnormal placentation. Defective invasion
of the spiral arteries by cytotrophoblast cells is observed
during pre-eclampsia. Recent studies have shown that
cytotrophoblast invasion of the uterus is actually a unique
differentiation pathway in which the fetal cells adopt certain attributes of the maternal endothelium they normally
replace. In pre-eclampsia, this differentiation process goes
awry.13 The abnormalities may be related to the nitric oxide
pathway, which contributes substantially to the control of
vascular tone. Moreover, inhibition of maternal synthesis
of nitric oxide prevents embryo implantation.14 Increased
uterine arterial resistance induces higher sensitivity to
vasoconstriction and thus chronic placental ischemia and
oxidative stress. This chronic placental ischemia causes fetal

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complications, including intrauterine growth retardation

and intrauterine death. In parallel, oxidative stress induces
release into the maternal circulation of substances such as
free radicals, oxidized lipids, cytokines, and serum soluble
vascular endothelial growth factor 1. These abnormalities
are responsible for endothelial dysfunction15 with vascular
hyperpermeability, thrombophilia, and hypertension, so as
to compensate for the decreased flow in the uterine arteries
due to peripheral vasoconstriction.
Endothelial dysfunction is responsible for the clinical
signs observed in the mother, ie, impairment of the hepatic
endothelium contributing to onset of the HELLP (Hemolysis,
Elevated Liver enzymes and Low Platelet count) syndrome,
impairment of the cerebral endothelium inducing refractory
neurological disorders, or even eclampsia. Depletion of
vascular endothelial growth factor in the podocytes makes
the endotheliosis more able to block the slit diaphragms in the
basement membrane, adding to decreased glomerular filtration and causing proteinuria. Finally, endothelial dysfunction
promotes microangiopathic hemolytic anemia, and vascular
hyperpermeability associated with low serum albumin causes
edema, particularly in the lower limbs or lungs.
The crucial issue to understand is that the prime mover
of pre-eclampsia is abnormal placentation. Two common
theories appear to be interlinked, ie, a genetic theory1,16 and an
immunological theory.17,18 Several susceptibility genes may
exist for pre-eclampsia.16,19 These genes probably interact in
the hemostatic and cardiovascular systems, as well as in the
inflammatory response. Some have been identified, and in
candidate gene studies they have provided evidence of linkage
to several genes, including angiotensinogen on 1-q4243 and
eNOS on 7q36; other main important loci are 2p12, 2p25,
9p13, and 10q22.1.16
Pre-eclampsia can be perceived as an impairment of the
maternal immune system that prevents it from recognizing
the fetoplacental unit. Excessive production of immune
cells causes secretion of tumor necrosis factor alpha which
induces apoptosis of the extravillous cytotrophoblast.17
The human leukocyte antigen (HLA) system also appears
to play a role in the defective invasion of the spiral arteries, in that women with pre-eclampsia show reduced levels
of HLA-G and HLA-E.18 During normal pregnancies, the
interaction between these cells and the trophoblast is due
to secretion of vascular endothelial growth factor and placental growth factor by natural killer cells. High levels of
soluble fms-like tyrosine kinase 1 (sFlt-1), an antagonist
of vascular endothelial growth factor and placental growth
factor, have been found in women with pre-eclampsia.17,18

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Accordingly, assays of sFlt-1, placental growth factor,

endoglin, and vascular endothelial growth factor, all of
which increase 48 weeks before onset of the disease, may
be useful predictors of pre-eclampsia. Recent data show the
protective role of heme oxygenase 1 and its metabolite, carbon monoxide, in pregnancy, and identify this as a potential
target in the treatment of pre-eclampsia.20

Clinical presentation and

workup findings
Clinical and laboratory tests are intended to define and
determine the severity of pre-eclampsia. Headaches, tinnitus,
phosphene signals, visual disorders, brisk tendon reflexes,
and vigilance disorders are related to cerebral edema; oliguria
to acute renal failure; uterine contraction, vaginal bleeding
to placental abruption; vomiting to HELLP syndrome; bandlike epigastric pain to subcapsular hepatic hematoma; and
dyspnea to cardiac failure. Eclampsia, the major neurological
complication of pre-eclampsia, is defined as a convulsive
episode or any other sign of altered consciousness arising in
a setting of pre-eclampsia, and which cannot be attributed to
a pre-existing neurological condition. Clinical examination
should include resting blood pressure measurement using
an appropriate cuff, and screening for weight gain, edema
(including signs of acute pulmonary edema and cerebral
edema), cardiomyopathy, and acute renal failure. The fetus
should be assessed by electrocardiotocography. Laboratory
tests include: a complete blood count with platelets, haptoglobin, and lactate dehydrogenase; a blood smear to test for
schistocytes; bilirubin, aspartate transaminase, and alanine
transaminase in order to identify potential HELPP syndrome;
electrolyte, urea, and creatinine assessment to check for acute
renal failure or uremia; 24-hour proteinuria; prothrombin,
activated thrombin time, and fibrinogen (microangiopathic
hemolytic anemia); blood group; and irregular antibody
screening. Other examinations include fetal ultrasound
with Doppler velocimetry of the umbilical, cerebral, and
uterine arteries, estimation of fetal weight, assessment of
fetal well-being by Manning score, and examination of the
placenta.21
Although the def inition of severe pre-eclampsia
varies,1,21,22 several components of this definition are usually
accepted: maternal systolic blood pressure $160mmHg or
diastolic blood pressure $110mmHg; maternal neurological
disorders such as persistent headaches, phosphene signals,
tinnitus, and brisk, diffuse, polykinetic tendon reflexes,
eclampsia, acute pulmonary edema, proteinuria $5g/day,
oliguria ,500 cc/day, creatinine .120 mol/L, HELLP

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Pre-eclampsia

s yndrome, thrombocytopenia ,100,000/mm3, and fetal

criteria, especially intrauterine growth retardation,
oligohydramnios, or fetal death in utero. Mild pre-eclampsia
is defined as diastolic blood pressure $90 mmHg measured on two occasions at least 6 hours apart, combined
with proteinuria (two or more occurrences of protein on
dipstick,.300mg total protein in a 24-hour urine collection,
or a protein creatinine ratio.30mg/mmol).1

Immediate emergency
management
Delivery is the only curative treatment for pre-eclampsia.1
Management is multidisciplinary, involving an obstetrician,
an anesthetist, and a pediatrician. In some cases consultation
of maternal fetal medicine and hypertension or nephrology
subspecialists may be required. Management decisions must
balance the maternal risks of continued pregnancy against
the fetal risks associated with induced preterm delivery.2
The criteria for delivery are based on two often interrelated
factors, ie, gestational age at diagnosis (estimated fetal
weight) and severity of pre-eclampsia.
Severe pre-eclampsia requires treatment with a dual
aim, ie, preventing the harmful effects of elevated maternal
blood pressure and preventing eclampsia. Management of
severe pre-eclampsia begins with transfer of the mother in a
fully equipped ambulance or helicopter to a maternity ward
providing an appropriate level of care for both mother and
child.2 At admission and daily thereafter, clinical, cardiotocographic, laboratory, and ultrasound testing are required to
detect the severity of pre-eclampsia and tailor management
accordingly.22
Regardless of the severity of pre-eclampsia, there is no
advantage in continuing the pregnancy when pre-eclampsia
is discovered after 3637 weeks. 2325 Nor is expectant
management justified for severe pre-eclampsia before
24 weeks, in view of the high risk of maternal complications
and the poor neonatal prognosis.2628 The obstetric team must
then discuss with the parents the possibility of a medical
interruption of pregnancy. Prolongation of pregnancy in
the event of mild pre-eclampsia can be discussed and reevaluated on a regular basis. At 34 37 weeks, management
depends on the severity of the pre-eclampsia. Expectant management is possible for mild pre-eclampsia to limit the risk
of induced preterm delivery, but for severe pre-eclampsia,
delivery remains the rule due to the increased risk of maternal
and fetal complications.2,22
Similarly, at 2434 weeks, management depends on
the severity of pre-eclampsia. The presence of one or

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more of the following signs indicates the need for immediate d elivery: uncontrolled severe hypertension (not
responsive to dual therapy), eclampsia, acute pulmonary
edema, abruptio placentae, subcapsular hepatic hematoma,
or t hrombocytopenia ,50,000/mm 3 . Delivery after
corticosteroid therapy for pulmonary maturation is necessary
if any of the following criteria is present: persistent epigastric
pain, signs of imminent eclampsia (headaches or persistent
visual disorders), de novo creatinine.120mol/L, oliguria
below 20mL/hour, progressive HELLP syndrome, prolonged
or severe variable decelerations with short-term variability
less than 3milliseconds. When emergency delivery is not
required, labor can be induced by cervical ripening.22
Antihypertensive treatment is useful only in severe preeclampsia because the sole proven benefit of such management
is to diminish the risk of maternal complications (cerebral
hemorrhage, eclampsia, or acute pulmonary edema).29 There is
no international consensus concerning antihypertensive treatment in pre-eclampsia. The four drugs authorized for the treatment of hypertension in severe pre-eclampsia in France are
nicardipine, labetalol, clonidine, and dihydralazine.29 There
is no ideal target blood pressure value, and too aggressive a
reduction in blood pressure is harmful to the fetus.30 Therapy
with a single agent is advised as first-line treatment, followed
by combination treatment when appropriate. The algorithm
for antihypertensive treatment proposed by French experts22
is shown in Figure1.
Pulmonary maturation using corticosteroids must be considered, taking gestational age into account. Betamethasone
remains the gold standard at a dosage of two injections of
12 mg 24 hours apart; this treatment reduces the risk of
hyaline membrane disease, intraventricular hemorrhage, and
neonatal mortality.31
Magnesium sulfate (MgSO4) may be part of the
therapeutic armamentarium for severe pre-eclampsia. It
is indicated in the treatment of eclamptic convulsions as
well as for secondary prevention of eclampsia, thus replacing treatment by diazepam, phenytoin, or the combination
of chlorpromazine, promethazine, and pethidine. 32 The
efficacy of MgSO4in the reduction of maternal and neonatal complications of eclampsia is well established. It is
administered intravenously, first at a loading dose of 4 g
over 1520minutes, which can be repeated at a half dose
(2g) if convulsion recurs, and then at a maintenance dose
of 1 g/hour for 24 hours.22,32 MgSO4 treatment must be
monitored in the intensive care unit because organ failure
may occur. This monitoring is based on repeated checking for a Glasgow score of 15, tendon reflexes, respiratory

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frequency.12 per minute, and diuresis.30mL/hour. Any

manifestation of overdose requires stopping the infusion,
considering injection of calcium gluconate, and measuring
blood magnesium levels.22
Eclampsia is generally considered an indication for
emergency cesarean section. Nonetheless, a decision to
delay a cesarean, albeit rare, may be based on fetal status
and justified if the mothers condition is stable and reassuring
after treatment.33

Management following delivery

Although delivery is the only effective treatment for
pre-eclampsia, and despite the fact that clinical symptoms
and laboratory abnormalities usually regress in the hours
afterwards, the risk of complications persists for some time
following delivery.6 Pre-eclampsia is associated with longterm morbidity and mortality. Approximately 20% of women
with pre-eclampsia develop hypertension or microalbuminuria during long-term follow-up, and the risk of subsequent
cardiovascular and cerebrovascular disease is doubled in
women with pre-eclampsia and gestational hypertension
compared with age-matched controls.34 A recent prospective
epidemiological study with a median follow-up duration of
30 years provides evidence that pre-eclampsia is a marker of
increased mortality from cardiovascular disease.35
Hemodynamic, neurological, and laboratory monitoring
is necessary following delivery for patients with severe preeclampsia.36 Hemodynamic monitoring includes frequent
blood pressure measurements to enable adjustment of antihypertensive treatment and frequent monitoring of diuresis
and weight according to intake (oliguria should prompt
progressive fluid resuscitation and sometimes diuretic use).
Neurological monitoring consists of checking for signs of
imminent eclampsia, including headaches, phosphene signals, tinnitus, and brisk tendon reflexes. Clinical monitoring must be done several times daily during the week after
delivery, a period considered at high risk for complications.
If necessary, monitoring can be performed in an intensive
care unit.
Laboratory monitoring should be done several times daily
in the first 72 hours after delivery and thereafter adapted
according to progress of the indices. It must include a
complete blood count, liver function tests, and measurement
of lactate dehydrogenase. Discharge from hospital cannot
be considered until all clinical and laboratory indices have
returned to normal, and regular monitoring by the patients
general practitioner as necessary if treatment for hypertension
is to be continued after discharge.

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Pre-eclampsia

SBP > 160 mmHg

SBP > 180 mmHg

or
DBP > 140 mmHg
Initiation of treatment

SBP < 180 mmHg

or
DBP < 140 mmHg
Maintenance treatment

Intravenous nicardipine
0.51 mg bolus
then
30 min of 4 to 7 mg perfusion

Nicardipine 16 mg/h
or
Intravenous labetalol 520 mg/h

After 30 minutes: Assessment of the therapeutic efficacy and tolerance

140 < SBP < 160 mmHg

100 < DBP < 120 mmHg
Maintenance treatment
nicardipine 16 mg/h
or
labetalol 520 mg/h

SBP > 160 mmHg

or
DBP > 120 mmHg
Bitherapy
Nicardipine 6 mg/h associated to :
Labetalol 520 mg/h
or
Clonidine 1540 g/h (if CI to )

Side effects
(cephalalgia, palpitations, etc)
Bitherapy
1. Reduction of nicardipine and
2. Association with:
Labetalol 520 mg/h
or
Clonidine 1540 g/h (if CI to )

SBP < 140 mmHg

DBP < 100 mmHg
Reduction or cessation
of the treatment

After 30 minutes and then every hour: reassessment of the therapeutic effect
Figure 1 Algorithm for antihypertensive treatment of pre-eclampsia.22
Note: MBP=[systolicBP +2diastolic BP]/3.
Abbreviations: MBP, mean blood pressure; CI, contraindication; SBP, systolic blood pressure; DBP, diastolic blood pressure.

The risk of recurrence of pre-eclampsia during a

subsequent pregnancy has to be considered. This risk is
estimated to be less than 10% for all cases of pre-eclampsia,37
but is greater when pre-eclampsia is discovered before
28 weeks. The relative risk is 15 if pre-eclampsia occurs at
2033weeks, 10 at 3336 weeks, and 8 after 37weeks.37
Three months after delivery, screening for underlying
renal or hypertensive disease may be requested by the
patients primary physician. Such screening is intended
to check for normalization of blood pressure values and
disappearance of proteinuria, and if abnormalities persist,

Vascular Health and Risk Management 2011:7

a referral should be made to a nephrologist or a hypertension

expert to determine the cause. This examination is important because pre-eclampsia may unmask previously
undiagnosed systemic or kidney disease or thrombophilia.
It should include a specific set of questions, blood pressure
measurement, a clinical examination looking for signs of
autoimmune conditions, and a urinary dipstick test. Testing
for antiphospholipid antibodies is recommended after severe
pre-eclampsia. The search for hereditary thrombophilia by
assays for protein C and S, antithrombin III, and a test for
resistance to activated protein C is recommended in the case

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Table 1 Major risk factors for pre-eclampsia49

Risk factor

OR or RR (95% CI)

Antiphospholipid antibody
syndrome
Renal disease
Prior pre-eclampsia
Systemic lupus erythematosus
Nulliparity
Chronic hypertension
Diabetes mellitus
High altitude
Multiple gestations
Strong family history of CV disease
(heart disease or stroke
in $2 first-degree relatives)
Obesity
Family history of pre-eclampsia
in first-degree relative
Advanced maternal age
(.40 years)

9.7 (4.321.7)
7.8 (2.228.2)
7.2 (5.88.8)
5.7 (2.016.2)
5.4 (2.810.3)
3.8 (3.44.3)
3.6 (2.55.0)
3.6 (1.111.9)
3.5 (3.04.2)
3.2 (1.47.7)

2.5 (1.73.7)
2.32.6 (1.83.6)
1.68 (1.232.29) for nulliparas
1.96 (1.342.87) for multparas

Abbreviations: CI, confidence interval; OR, odds ratio; RR, relative risk; CV,
cardiovascular.

of a personal or family history of venous thromboembolic

disease, early pre-eclampsia, or pre-eclampsia with any
intrauterine growth retardation, abruptio placentae, or in utero
death.22,38 Percutaneous needle biopsy of the kidney should
be performed only if kidney failure persists at three months
postpartum or if signs of a systemic underlying condition or
proteinuria persist at 6months.23
Patients who have had severe pre-eclampsia may
share predispositions with nonpregnant patients who
have cardiovascular risk factors.39 Accordingly, long-term
monitoring of cardiovascular, renal, and metabolic risk
factors is recommended after severe pre-eclampsia.22

Prevention
Primary prevention of pre-eclampsia is based on the detection
of modifiable risk factors. The literature is plentiful regarding the risk factors for pre-eclampsia, but should be interpreted with caution.48 Women at high risk are those with a
personal history of severe pre-eclampsia, while those at low
risk are defined as those who have never had pre-eclampsia
but have at least one risk factor.2 There are numerous risk
factors,48 including genetic risk factors, family history of
pre-eclampsia, immunologic factors, nulliparity, a new partner, and demographic factors such as a maternal age.35
years, the womans own gestational age and birth weight (with
elevated risks for women born before 34 weeks or weighing
less than 2500g at birth), factors related to the pregnancy,
such as multiple pregnancy, congenital or chromosomal
anomalies, a hydatidiform mole, or urinary infection, risk

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factors associated with maternal disease, including chronic

hypertension, kidney disease, obesity, insulin resistance,
and diabetes, as well as thrombophilia, and environmental
factors such as living at a high altitude and stress. Although
the search for these risk factors is important, they may not
effectively predict this pre-eclampsia by themselves.
However, accurate prediction of pre-eclampsia would
enable early and optimal management of women at high risk.
Several predictive tests are being assessed currently. These
include clinical tests, such as blood pressure measurement
during the second trimester or 24-hour ambulatory blood pressure monitoring, but these lack sensitivity and specificity.40
Laboratory tests for oxidative response have been assessed,
including assays for uric acid, urinary kallikrein, and
fibronectin, but no evidence of their relevance has so far
been found.40 Among the markers used to screen for trisomy 21 during the second trimester (beta human chorionic
gonadotropin, alpha fetoprotein, and unconjugated estriol),
elevated alpha fetoprotein is associated with a higher risk of
pre-eclampsia (unless there are neural tube abnormalities,
as when beta human chorionic gonadotropin is elevated).
Frequent monitoring of women with elevated levels could
be useful, but these tests may not be carried out for screening
purposes due to their low negative predictive value.40 Serum
markers for trisomy 21 in the first trimester (pregnancyassociated plasma protein A, inhibin A, corticotropinreleasing hormone, and activin) have been tested, but their
likelihood ratios seem to be insufficient.
Imaging tests have been evaluated, including uterine
artery Doppler ultrasound.41,42 Uterine artery Doppler ultrasound is not advised during the first or second trimester
in low-risk populations due to the excessive variability
of likelihood ratios in this population, which allows for
the prediction of only one-third of pre-eclampsia cases.43
In a high-risk population, the definition of which is often
imprecise, uterine artery Doppler can be performed during
the second trimester morphologic ultrasound examination
and checked 1 month later in case of abnormal results
(resistance index.0.58 or 9095th percentile, unilateral
or bilateral notch). The combination of a uterine artery
Doppler examination during the first trimester and a
three-dimensional ultrasound assessing placental volume
may predict the risk of pre-eclampsia as early as the first
trimester.44
In clinical practice, because no single marker effectively
predicts the risk of pre-eclampsia, the current trend is to
test a combination of markers. The most commonly used
combination of markers assesses sFlt-1, placental growth

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f actor, endoglin, and vascular endothelial growth factor

during the first or second trimester. Increased vascular
endothelial growth factor and endoglin levels, combined
with increased sFlt-1 and decreased placental growth factor
during the first trimester, is associated with a significantly
increased risk of pre-eclampsia.20
Improved prediction of pre-eclampsia has been noticed
when serum markers are combined with Doppler indices. In a
recent nested case-control study, second trimester maternal
serum cystatin C, C-reactive protein, and uterine artery mean
resistance index were observed to be independent predictors
of pre-eclampsia.45
Secondary prevention is based on antiplatelet aspirin
therapy, which reduces the risk of pre-eclampsia by 10%
in women who have at least one risk factor.46 No study
currently allows determination of the exact dosage or the
best time for initiation of aspirin. However, aspirin should
be initiated as early as possible, ie, before 1214weeks,
which corresponds to the beginning of the first phase of
trophoblast invasion. The efficacy of aspirin has been
shown only in women with previous pre-eclampsia associated with intrauterine growth retardation and without
thrombophilia. Low molecular weight heparin is indicated
only in cases of complicated thrombophilia (history of
thromboembolic complications or of pre-eclampsia). 47
Calcium supplementation at a dosage of 1.5g/day, beginning at 15 weeks and continued throughout the pregnancy,
is recommended for prevention of pre-eclampsia in women
with a daily calcium intake ,600 mg/day.48 The statins,
which stimulate HO-1 expression and inhibit sFlt-1
release, could have the potential to ameliorate early-onset
pre-eclampsia.20 Other treatments, such as antioxidant
treatment by vitamins C and E, oligoelements, and nitric
oxide have no proven efficacy.6

Conclusion
Pre-eclampsia is a rare pregnancy-related disease with an
unpredictable course that can have serious consequences
for both the mother and the fetus. The treatment is simple, ie, delivery. Nonetheless, induced preterm delivery
requires careful weighing of both maternal and fetal risk
benefit. Accordingly, identifying delivery criteria in case of
pre-eclampsia is crucial to optimal management. Current
research focuses on the prediction of onset of pre-eclampsia
or even severe pre-eclampsia so as to allow early management and improve the morbidity and mortality associated
with this disease. Specific tools for secondary prevention
must also be developed for recurrent pre-eclampsia.

Vascular Health and Risk Management 2011:7

Pre-eclampsia

Disclosure
The authors report no conflicts of interest in this work.

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