Curr Hypertens Rep (2014) 16:473
DOI 10.1007/s11906-014-0473-5
PREECLAMPSIA (VD GAROVIC, SECTION EDITOR)
Treatment of Preeclampsia: Current Approach
and Future Perspectives
Ecaterina Berzan & Ross Doyle & Catherine M. Brown
Published online: 19 August 2014
# Springer Science+Business Media New York 2014
Abstract Hypertension is the most common medical disorder
encountered during pregnancy, occurring in about 68 % of
pregnancies. Preeclampsia is a pregnancy-specific disorder
that occurs after 20 weeks gestation, characterized by hyper-
tension and proteinuria. Preeclampsia can also occur
superimposed upon chronic hypertension. Eclampsia is the
convulsive form of preeclampsia, and affects 0.1 % of all
pregnancies. In low-income and middle-income countries,
preeclampsia and eclampsia are associated with 1015 % of
direct maternal deaths. Women who develop preeclampsia in
pregnancy are at greater risk of cardiovascular and cerebro-
vascular events even years after their pregnancies. There is
significant progress in the elucidation of the underlying mech-
anisms and pathophysiology of preeclampsia, although its
therapeutics remains challenging; delivery of the fetus is still
the definitive treatment. Different international societies have
produced recommendations and guidelines for clinicians
treating preeclampsia, with an overall goal of improving ma-
ternal and fetal outcomes. In this review, we focus on the level
of blood pressure at which to commence treatment and the
current clinical management strategies available to treat and
possibly prevent preeclampsia. We also briefly outline some
newer perspectives on management of the disorder.
Keywords Hypertension . Pregnancy . Preeclampsia .
Antihypertensives . Low-dose aspirin . Magnesium sulphate .
Guidelines
This article is part of the Topical Collection on Preeclampsia
E. Berzan : R. Doyle : C. M. Brown (*)
Department of Nephrology, University Hospital Waterford, Dunmore
Road, Waterford, Ireland
e-mail: CatherineM.Brown@hse.ie
Introduction
Hypertension in pregnancy is classified as chronic hyperten-
sion, preeclampsia-eclampsia, preeclampsia superimposed
upon chronic hypertension, and gestational hypertension
[13]. Worldwide, it is estimated that hypertensive disor-
ders in pregnancy account for 14 % of all maternal deaths
[4]. Preeclampsia, a pregnancy-specific disorder involv-
ing multiple organ systems, is characterized by hyperten-
sion (140/90 mm Hg) and proteinuria (300 mg in a 24-
hour urine), and affects 34 % of all pregnancies world-
wide. It is unique to pregnancy and can occur antepartum,
intrapartum, or postpartum. It may also develop
superimposed upon chronic hypertension. The definitions
of hypertension in pregnancy from different international
groups are outlined in Table 1. Recent debate on the
diagnosis of preeclampsia has suggested that a subclass
of non-proteinuric preeclampsia may occur [11] or that
proteinuria should not be mandatory for a diagnosis of
preeclampsia [12]. Risk factors for the development of
preeclampsia include primiparity, previous preeclampsia,
multiple gestations, ethnicity (black women are at elevat-
ed risk), elevated body mass index (BMI) before pregnan-
cy, and underlying medical conditions such as renal dys-
function, hypertension, and diabetes mellitus [13].
The pathophysiology of preeclampsia includes abnormal
placentation and dysfunctional trophoblast development, de-
fective placental angiogenesis, and a heightened systemic
inflammatory response in the mother [1417]. Women with
mild forms of preeclampsia generally have uneventful deliv-
eries, while women with more severe forms can develop
features such as renal involvement, neurological sequelae,
eclampsia, and HELLP syndrome (hemolysis, elevated liver
enzymes, and low platelet count). In extreme cases, maternal
death can occur, preceded by acute renal failure, hepatic
rupture, pulmonary edema, placental abruption, seizure, and
473, Page 2 of 6 Curr Hypertens Rep (2014) 16:473

Table 1 Guidelines for diagnosis of hypertension in pregnancy and blood pressure treatment levels (adapted from [5])

Guideline Definition of hypertension in pregnancy Recommended blood pressure treatment level

SOGC [6] A. Pre-existing hypertension (before pregnancy or <20 wks.
gestation)
(1) with comorbid conditions (2) with preeclampsia (hypertension,
proteinuria, and adverse conditions, >20 weeks gestation)
B. Gestational hypertension (20 wks.)
(1) with comorbid conditions (2) with preeclampsia (hypertension,
proteinuria, and adverse conditions)
ESH/ESC [7, 8] A. Pre-existing hypertension
B. Preeclampsia- gestational hypertension with significant
proteinuria
C. Gestational hypertension
D. Pre-existing hypertension plus superimposed gestational
hypertension with proteinuria
E. Antenatally unclassifiable hypertension- postpartum re-
classified as
(1) gestational hypertension with or without proteinuria
(2) pre-existing hypertension
NICE [9] A. Primary or secondary chronic hypertension
<20 weeks gestation or on antihypertensive meds before referral
to maternity service
B. Preeclampsia- new hypertension>20 weeks with significant
proteinuria
(1) mild, (2) moderate, (3) severe hypertension
Eclampsia (convulsive condition associated with preeclampsia)
C. Gestational hypertension new hypertension>20 weeks without
significant proteinuria
(1) mild, (2) moderate, (3) severe hypertension
SOMANZ [10] A. Chronic hypertension
(1) essential, (2) secondary, or (3) white-coat
B. Preeclampsia-eclampsia
C. Gestational hypertension
D. Preeclampsia superimposed upon chronic hypertension
Severe HTN (>160/110 mmHg), BP should be lowered to
<160 mmHg SBP and <110 mmHg DBP
Non-severe HTN (140159/90109 mmHg), BP should be
lowered to 130155 mmHg SBP and 80105 mmHg DBP
when there are no comorbid conditions
For women with comorbidities, SBP should be lowered to 130
139 mmHg and DBP to 8089 mmHg
Drug treatment of severe HTN in pregnancy (SBP >160 mmHg
or DBP >110 mmHg) is recommended
Drug treatment may also be considered in pregnant women with
persistent elevation of BP 150/95 mmHg, and in those with
BP 140/ 90 mmHg in the presence of GHTN, subclinical
organ damage or symptoms
In pregnant women with uncomplicated chronic HTN, aim to
keep blood pressure lower than 150/100 mmHg
Do not lower diastolic blood pressure below 80 mmHg
Offer pregnant women with target organ damage secondary to
chronic HTN (e.g., kidney disease) treatment with the aim of
keeping BP lower than 140/90 mmHg
In preeclampsia and GHTN, treat only if BP 150/100 mmHg
Antihypertensive treatment should be commenced in all women
with SBP 170 mmHg or DBP 110 mmHg
Treatment for mild to moderate HTN of 140160/ 90
100 mmHg is optional and will reflect local practice

BP, blood pressure; GHTN, gestational hypertension; HTN, hypertension, SOGC, Society of Obstetricians and Gynaecologists of Canada; ESH/ESC,
European Society of Hypertension/European Society of Cardiology; NICE, National Institute for Health and Clinical Excellence; SOMANZ, Society of
Obstetric Medicine of Australia and New Zealand.

coma. Adverse fetal outcomes include premature delivery,
growth retardation, and death. Treatment of severe hyperten-
sion is necessary to prevent maternal cerebrovascular, cardiac,
and renal complications.
Preeclampsia: When to Treat the Blood Pressure
The National High Blood Pressure Education Program
(NHBPEP) Working Group Report on High Blood Pres-
sure in Pregnancy guidelines states that a normal or ac-
ceptable blood pressure in pregnancy is SBP of 140 and
DBP of 90 mm Hg. Mild hypertension is defined as SBP
of 140150 or DBP of 90109 mm Hg, and severe hy-
pertension is defined as SBP of 160 or DBP of
110 mm Hg [1]. In preeclampsia, antihypertensive ther-
apy can be withheld unless there is persistent DBP of
105110 mmHg or higher. The American College of
Obstetricians and Gynecologists (ACOG) recently
convened a task force on hypertension in pregnancy, and
has provided current recommendations for treatment
[18]. The guidelines state that for women with mild
preeclampsia (SBP<160 mm Hg or DBP<110 mm Hg),
antihypertensives are not recommended (the quality of
this evidence is moderate and the strength of this recom-
mendation is qualified). Antihypertensive therapy is rec-
ommended for women with preeclampsia and a sustained
SBP of 160 mm Hg or DBP of 110 mm Hg (the quality
of this evidence is moderate and the strength of this
recommendation is strong).
There is much discussion with regard to the level of blood
pressure at which to start treatment. Recommendations from
the Society of Obstetricians and Gynaecologists of Canada
(SOGC), the European Society of Hypertension/European
Society of Cardiology (ESH/ESC), the National Institute for
Health and Clinical Excellence (NICE) UK, and the Society of
Obstetric Medicine of Australia and New Zealand
(SOMANZ) are outlined in Table 1.
Curr Hypertens Rep (2014) 16:473 Page 3 of 6, 473

Preeclampsia: What Treatments to Use
Antihypertensive Therapies
An overview of some of the commonly used antihypertensives
in pregnancy is presented in Table 2. According to the
NHBPEP, methyldopa, labetalol, beta blockers (other than
atenolol), and slow-release nifedipine are considered appropri-
ate treatments [1]. For emergency treatment in preeclampsia, IV
hydralazine, labetalol, and oral nifedipine can be used [1]. The
ACOG Practice Bulletins also identify methyldopa and
labetalol as appropriate first-line agents, and beta blockers and
angiotensin-converting enzyme inhibitors are not recommend-
ed [2, 3].
Severe hypertension in preeclampsia is defined as BP
160 mm Hg systolic, DBP105 mm Hg diastolic, or both.
There are several recommended treatment options in this
scenario [1]. Hydralazine can be given intravenously (IV) at

Table 2 Treatment therapies for hypertension in pregnancy (adapted from [5])

Drug treatment Dose, daily [19, 20] Side effects and safety profile

First-line agents
Methyldopa 0.53 gm/day in 2 divided doses po Proven safety and efficacy
Drug of choice according to all groups Some concern with depression, hepatic disturbances,
hemolytic anemia may not lower BP adequately
FDA class B; Compatible with breast milk
Labetalol 2001200 mg/day po in 23 divided doses Safety similar to methyldopa may be more efficacious
2040 mg iv (max 220 mg total) than methyldopa;
May be associated with fetal growth restriction. Neonatal
hypoglycemia with larger doses
FDA class C; Usually compatible with breast milk
Second-line agents
Nifedipine (long-acting) 1030 mg po Widely used
May inhibit labor
Rarely, profound hypotension if short-acting agent is used
with magnesium
FDA class C; Usually compatible with breast milk
Verapamil 80 mg tid po Similar efficacy to other oral agents
Risk of interaction with magnesium bradycardia
FDA class C; Usually compatible with breast milk
Clonidine 0.10.6 mg/day in 2 divided doses Safety similar to methyldopa
Limited data regarding fetal safety
Efficacy similar to methyldopa
FDA class C; Possible breast milk effects
Alternative options
Hydralazine 50300 mg/day in 24 divided doses Efficacious intravenous agent
Not recommended by ESH [7, 8] Possible maternal polyneuropathy, drug-induced lupus,
neonatal lupus and thrombocytopenia Tachyphylaxis
FDA class D; Usually compatible with breast milk
Diazoxide 3050 mg iv every 515 min; iv bolus for acute BP lowering in severe hypertension [10]
Prazosin 0.55 mg tid; considered as a second-line agent by SOMANZ [10]
Not recommended by SOGC [6]
Associated with postural hypotension and palpitations
Oxprenolol (beta blocker with ISA) 20160 mg tid; considered as a first-line agent by SOMANZ [10]
Contraindicated in heart block
Nitroprusside Only considered for life-threatening severe hypertension
Cyanide and thiocyanate toxicity, must be carefully monitored
Also risk of cardio-neurogenic syncope
Contraindicated [19] Atenolol not recommended, risk of growth restriction when started in first or second trimester and is not
recommended if breastfeeding
ACE inhibitors, angiotensin II receptor blockers
Direct renin inhibitors
Spironolactone not recommended due to potential foetal anti-androgen effects

Breastfeeding compatibility: according to the World Health Organization and/or Thomson lactation ratings. FDA, Food and Drug Administration; ISA,
intrinsic sympathomimetic activity; ACE, angiotensin-converting enzyme; po, per oral; tid, three times per day
473, Page 4 of 6
5 mg, or 10 mg intramuscularly (IM). A dose of 510 mg can
be repeated at 20-minute intervals as needed. If there is no
response in blood pressure after 20 mg IV or 30 mg IM, then
another agent can be considered. Labetalol 20 mg IV as a
bolus can be given in this setting, with a further 40 mg
10 minutes later if needed, followed by two further doses at
80 mg 10 minutes apart, to a maximum dose of 220 mg.
Again, if the blood pressure response is not achieved, an
alternative agent can be used. Long-acting nifedipine can be
given orally at 10 mg to start, repeating after 30 minutes if
required. In rare cases where the woman is not responding to
any of these three drugs or there is evidence of hypertensive
encephalopathy, sodium nitroprusside can be considered,
starting at 0.25 g/kg/minute, to a maximum dose of 5 g/
kg/minute [1]. If used for longer than four hours, fetal cyanide
poisoning is a risk.
Other Management Strategies
Magnesium sulphate plays an important role in the manage-
ment of preeclampsia/eclampsia. It more than halves the risk
of eclampsia, and probably reduces maternal death [21]. In
women with fulminant eclampsia, magnesium sulphate re-
duces the risk ratio of maternal death and recurrence of sei-
zures compared with diazepam [22].
The use of low-dose aspirin in women at increased risk of
preeclampsia has been well-investigated. Low doses of aspirin
reduce the risk of preeclampsia by 17 %, the risk of fetal or
neonatal death by 14 %, and the relative risk of preterm birth by
8 % [23]. Guidelines suggest that women at high risk of pre-
eclampsia (hypertension in a previous pregnancy, chronic kid-
ney disease, autoimmune diseases such as systemic lupus ery-
thematosus, and antiphospholipid syndrome, type 1 or 2 diabe-
tes or chronic hypertension) or with more than one moderate risk
factor for preeclampsia (first pregnancy, age>40 years, pregnan-
cy interval of >10 years, BMI >35 kg/m2 at first visit, family
history of preeclampsia, and multiple pregnancies) should be
advised to take 75 mg of aspirin daily from the 12th week until
delivery [7]. The UK NICE guidelines recommend aspirin
75 mg/day over the same period of time for women who have
at least two moderate risk factors (as listed above) or at least one
high risk factor (as listed above) for preeclampsia. [9].
Calcium supplementation during pregnancy for preventing
hypertensive disorders has been suggested in studies to lower
the risk of preeclampsia by approximately half, as well as
reduce the risk of preterm birth and the rare occurrence of the
composite outcome: death or serious morbidity [24]. The
women participating in these trials were fed a low-calcium
diet and were supplemented with at least 1 g of calcium daily.
The evidence for added calcium in the prevention of hyper-
tensive disorders, however, is conflicting [25].
Some studies have reported an association between vitamin
D deficiency and increased risk for preeclampsia [26]. A
Curr Hypertens Rep (2014) 16:473
systematic review of randomized controlled trials evaluated
the effect of vitamin D supplementation and pregnancy out-
come. The data showed that supplementation with vitamin D
did not reduce the incidence of preeclampsia or its complica-
tions [27]. There is also no evidence that supplementation
with vitamins C and E reduces the rate of serious adverse
outcomes of preeclampsia among low-risk nulliparous women
[28]. The preeclamptic placenta displays characteristic fea-
tures of uteroplacental ischemia. It has been suggested that
fish oil may have protective vascular and antihypertensive
effects [29]. A meta-analysis of trials investigating fish oil
supplementation for the prevention of preeclampsia failed to
prove its efficacy at reducing the incidence of preeclampsia
[30]. Fish oil supplementation and vitamin and nutrient sup-
plements appear to have no benefit in the prevention of
hypertensive disorders [31].
Maternal obesity is a known risk factor for preeclampsia.
Few studies have investigated the impact of weight loss on the
risk for developing preeclampsia. There is some evidence that
weight loss following bariatric surgery or between pregnan-
cies significantly reduced the risk of developing preeclampsia
[32, 33]. Bed rest and rest at home are not recommended as
part of the prevention of or treatment for preeclampsia [34,
35]. Dietary salt intake does not appear to play a role in
preventing preeclampsia [36], and steroid therapy is recom-
mended only after fetal lung maturation [6, 9, 10].
Preeclampsia: Future Perspectives
It has been proposed that preeclamptic women might be
deficient in nitric oxide, a vasodilator and inhibitor of platelet
aggregation [37]. L-arginine, the substrate for the synthesis of
nitric oxide, has been proposed as playing a role in preventing
preeclampsia. A recent systematic review of randomized con-
trolled trials investigated the use of L-arginine for the preven-
tion and treatment of preeclampsia. For women at risk of
preeclampsia and with established hypertensive disease, L-
arginine was associated with reduction in preeclampsia and
preterm births when compared with placebo [38].
Future therapeutic targets in preeclampsia include the path-
ways involved in angiogenesis, attempting to restore the an-
giogenic balance in the placenta, as well as reducing oxidative
stress [39, 40]. PARP inhibitors have been shown to prevent
the development of both endothelial dysfunction and hyper-
tension [41] in rat models of preeclampsia and may prove to
have therapeutic value.
There is evidence of an association between dysregulated
pro-angiogenic factors, hypertension, and podocyte injury.
Further examination of the mechanism of podocyte injury
and detachment may identify novel therapeutic targets [42].
Curr Hypertens Rep (2014) 16:473
New guidelines for the prevention of stroke, specifically in
women, have been put forward by the American Heart
Association/American Stroke Association (AHA/ASA) [43].
Recommendations include the use of prophylactic aspirin and/
or calcium supplements in women with a history of hyperten-
sion to prevent preeclampsia. They also suggest that women
who have had preeclampsia should undergo postpartum screen-
ing for any modifiable cardiovascular risk factors and receive
appropriate treatment. Finally, they suggest considering treat-
ment of moderately high blood pressure (150219/100
109 mm Hg), although this may prove controversial [44].
Conclusions
It is estimated that hypertensive disorders in pregnancy ac-
count for 14 % of all maternal deaths [4]. Over the last
decade, new evidence has emerged with respect to the patho-
physiology of preeclampsia, although this has not yet been
incorporated into the development of therapeutic targets.
There are numerous guidelines and recommendations
available to the clinician treating preeclampsia. Management
includes control of blood pressure with antihypertensives, the
use of low-dose aspirin for prevention, and magnesium sul-
phate when indicated. Delivery remains the only definitive
treatment. We would also suggest that management should
include the continued treatment of women with a remote
history of preeclampsia. We believe that the treatment of
preeclampsia does not end after pregnancy, or even after the
childbearing years. These women need to be followed in later
life for the development of cardiovascular disease risk, and
advised and treated for any modifiable risk factors.
Compliance with Ethics Guidelines
Conflict of Interest Ecaterina Berzan, Ross Doyle, and Catherine M.
Brown each declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
of the authors.
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