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Curr Hypertens Rep (2014) 16:473

DOI 10.1007/s11906-014-0473-5


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 Introduction

encountered during pregnancy, occurring in about 68 % of
pregnancies. Preeclampsia is a pregnancy-specific disorder Hypertension in pregnancy is classified as chronic hyperten-
that occurs after 20 weeks gestation, characterized by hyper- sion, preeclampsia-eclampsia, preeclampsia superimposed
tension and proteinuria. Preeclampsia can also occur upon chronic hypertension, and gestational hypertension
superimposed upon chronic hypertension. Eclampsia is the [13]. Worldwide, it is estimated that hypertensive disor-
convulsive form of preeclampsia, and affects 0.1 % of all ders in pregnancy account for 14 % of all maternal deaths
pregnancies. In low-income and middle-income countries, [4]. Preeclampsia, a pregnancy-specific disorder involv-
preeclampsia and eclampsia are associated with 1015 % of ing multiple organ systems, is characterized by hyperten-
direct maternal deaths. Women who develop preeclampsia in sion (140/90 mm Hg) and proteinuria (300 mg in a 24-
pregnancy are at greater risk of cardiovascular and cerebro- hour urine), and affects 34 % of all pregnancies world-
vascular events even years after their pregnancies. There is wide. It is unique to pregnancy and can occur antepartum,
significant progress in the elucidation of the underlying mech- intrapartum, or postpartum. It may also develop
anisms and pathophysiology of preeclampsia, although its superimposed upon chronic hypertension. The definitions
therapeutics remains challenging; delivery of the fetus is still of hypertension in pregnancy from different international
the definitive treatment. Different international societies have groups are outlined in Table 1. Recent debate on the
produced recommendations and guidelines for clinicians diagnosis of preeclampsia has suggested that a subclass
treating preeclampsia, with an overall goal of improving ma- of non-proteinuric preeclampsia may occur [11] or that
ternal and fetal outcomes. In this review, we focus on the level proteinuria should not be mandatory for a diagnosis of
of blood pressure at which to commence treatment and the preeclampsia [12]. Risk factors for the development of
current clinical management strategies available to treat and preeclampsia include primiparity, previous preeclampsia,
possibly prevent preeclampsia. We also briefly outline some multiple gestations, ethnicity (black women are at elevat-
newer perspectives on management of the disorder. ed risk), elevated body mass index (BMI) before pregnan-
cy, and underlying medical conditions such as renal dys-
function, hypertension, and diabetes mellitus [13].
Keywords Hypertension . Pregnancy . Preeclampsia . The pathophysiology of preeclampsia includes abnormal
Antihypertensives . Low-dose aspirin . Magnesium sulphate . placentation and dysfunctional trophoblast development, de-
Guidelines 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
This article is part of the Topical Collection on Preeclampsia features such as renal involvement, neurological sequelae,
eclampsia, and HELLP syndrome (hemolysis, elevated liver
E. Berzan : R. Doyle : C. M. Brown (*)
enzymes, and low platelet count). In extreme cases, maternal
Department of Nephrology, University Hospital Waterford, Dunmore
Road, Waterford, Ireland death can occur, preceded by acute renal failure, hepatic
e-mail: CatherineM.Brown@hse.ie 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. Severe HTN (>160/110 mmHg), BP should be lowered to
gestation) <160 mmHg SBP and <110 mmHg DBP
(1) with comorbid conditions (2) with preeclampsia (hypertension, Non-severe HTN (140159/90109 mmHg), BP should be
proteinuria, and adverse conditions, >20 weeks gestation) lowered to 130155 mmHg SBP and 80105 mmHg DBP
B. Gestational hypertension (20 wks.) when there are no comorbid conditions
(1) with comorbid conditions (2) with preeclampsia (hypertension, For women with comorbidities, SBP should be lowered to 130
proteinuria, and adverse conditions) 139 mmHg and DBP to 8089 mmHg
ESH/ESC [7, 8] A. Pre-existing hypertension Drug treatment of severe HTN in pregnancy (SBP >160 mmHg
B. Preeclampsia- gestational hypertension with significant or DBP >110 mmHg) is recommended
proteinuria Drug treatment may also be considered in pregnant women with
C. Gestational hypertension persistent elevation of BP 150/95 mmHg, and in those with
D. Pre-existing hypertension plus superimposed gestational BP 140/ 90 mmHg in the presence of GHTN, subclinical
hypertension with proteinuria organ damage or symptoms
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 In pregnant women with uncomplicated chronic HTN, aim to
<20 weeks gestation or on antihypertensive meds before referral keep blood pressure lower than 150/100 mmHg
to maternity service Do not lower diastolic blood pressure below 80 mmHg
B. Preeclampsia- new hypertension>20 weeks with significant Offer pregnant women with target organ damage secondary to
proteinuria chronic HTN (e.g., kidney disease) treatment with the aim of
(1) mild, (2) moderate, (3) severe hypertension keeping BP lower than 140/90 mmHg
Eclampsia (convulsive condition associated with preeclampsia) In preeclampsia and GHTN, treat only if BP 150/100 mmHg
C. Gestational hypertension new hypertension>20 weeks without
significant proteinuria
(1) mild, (2) moderate, (3) severe hypertension
SOMANZ [10] A. Chronic hypertension Antihypertensive treatment should be commenced in all women
(1) essential, (2) secondary, or (3) white-coat with SBP 170 mmHg or DBP 110 mmHg
B. Preeclampsia-eclampsia Treatment for mild to moderate HTN of 140160/ 90
C. Gestational hypertension 100 mmHg is optional and will reflect local practice
D. Preeclampsia superimposed upon chronic hypertension

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, convened a task force on hypertension in pregnancy, and
growth retardation, and death. Treatment of severe hyperten- has provided current recommendations for treatment
sion is necessary to prevent maternal cerebrovascular, cardiac, [18]. The guidelines state that for women with mild
and renal complications. 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-
Preeclampsia: When to Treat the Blood Pressure mendation is qualified). Antihypertensive therapy is rec-
ommended for women with preeclampsia and a sustained
The National High Blood Pressure Education Program SBP of 160 mm Hg or DBP of 110 mm Hg (the quality
(NHBPEP) Working Group Report on High Blood Pres- of this evidence is moderate and the strength of this
sure in Pregnancy guidelines states that a normal or ac- recommendation is strong).
ceptable blood pressure in pregnancy is SBP of 140 and There is much discussion with regard to the level of blood
DBP of 90 mm Hg. Mild hypertension is defined as SBP pressure at which to start treatment. Recommendations from
of 140150 or DBP of 90109 mm Hg, and severe hy- the Society of Obstetricians and Gynaecologists of Canada
pertension is defined as SBP of 160 or DBP of (SOGC), the European Society of Hypertension/European
110 mm Hg [1]. In preeclampsia, antihypertensive ther- Society of Cardiology (ESH/ESC), the National Institute for
apy can be withheld unless there is persistent DBP of Health and Clinical Excellence (NICE) UK, and the Society of
105110 mmHg or higher. The American College of Obstetric Medicine of Australia and New Zealand
Obstetricians and Gynecologists (ACOG) recently (SOMANZ) are outlined in Table 1.
Curr Hypertens Rep (2014) 16:473 Page 3 of 6, 473

Preeclampsia: What Treatments to Use hydralazine, labetalol, and oral nifedipine can be used [1]. The
ACOG Practice Bulletins also identify methyldopa and
Antihypertensive Therapies labetalol as appropriate first-line agents, and beta blockers and
angiotensin-converting enzyme inhibitors are not recommend-
An overview of some of the commonly used antihypertensives ed [2, 3].
in pregnancy is presented in Table 2. According to the Severe hypertension in preeclampsia is defined as BP
NHBPEP, methyldopa, labetalol, beta blockers (other than 160 mm Hg systolic, DBP105 mm Hg diastolic, or both.
atenolol), and slow-release nifedipine are considered appropri- There are several recommended treatment options in this
ate treatments [1]. For emergency treatment in preeclampsia, IV 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 Curr Hypertens Rep (2014) 16:473

5 mg, or 10 mg intramuscularly (IM). A dose of 510 mg can systematic review of randomized controlled trials evaluated
be repeated at 20-minute intervals as needed. If there is no the effect of vitamin D supplementation and pregnancy out-
response in blood pressure after 20 mg IV or 30 mg IM, then come. The data showed that supplementation with vitamin D
another agent can be considered. Labetalol 20 mg IV as a did not reduce the incidence of preeclampsia or its complica-
bolus can be given in this setting, with a further 40 mg tions [27]. There is also no evidence that supplementation
10 minutes later if needed, followed by two further doses at with vitamins C and E reduces the rate of serious adverse
80 mg 10 minutes apart, to a maximum dose of 220 mg. outcomes of preeclampsia among low-risk nulliparous women
Again, if the blood pressure response is not achieved, an [28]. The preeclamptic placenta displays characteristic fea-
alternative agent can be used. Long-acting nifedipine can be tures of uteroplacental ischemia. It has been suggested that
given orally at 10 mg to start, repeating after 30 minutes if fish oil may have protective vascular and antihypertensive
required. In rare cases where the woman is not responding to effects [29]. A meta-analysis of trials investigating fish oil
any of these three drugs or there is evidence of hypertensive supplementation for the prevention of preeclampsia failed to
encephalopathy, sodium nitroprusside can be considered, prove its efficacy at reducing the incidence of preeclampsia
starting at 0.25 g/kg/minute, to a maximum dose of 5 g/ [30]. Fish oil supplementation and vitamin and nutrient sup-
kg/minute [1]. If used for longer than four hours, fetal cyanide plements appear to have no benefit in the prevention of
poisoning is a risk. hypertensive disorders [31].
Maternal obesity is a known risk factor for preeclampsia.
Other Management Strategies Few studies have investigated the impact of weight loss on the
risk for developing preeclampsia. There is some evidence that
Magnesium sulphate plays an important role in the manage- weight loss following bariatric surgery or between pregnan-
ment of preeclampsia/eclampsia. It more than halves the risk cies significantly reduced the risk of developing preeclampsia
of eclampsia, and probably reduces maternal death [21]. In [32, 33]. Bed rest and rest at home are not recommended as
women with fulminant eclampsia, magnesium sulphate re- part of the prevention of or treatment for preeclampsia [34,
duces the risk ratio of maternal death and recurrence of sei- 35]. Dietary salt intake does not appear to play a role in
zures compared with diazepam [22]. preventing preeclampsia [36], and steroid therapy is recom-
The use of low-dose aspirin in women at increased risk of mended only after fetal lung maturation [6, 9, 10].
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- Preeclampsia: Future Perspectives
ney disease, autoimmune diseases such as systemic lupus ery-
thematosus, and antiphospholipid syndrome, type 1 or 2 diabe- It has been proposed that preeclamptic women might be
tes or chronic hypertension) or with more than one moderate risk deficient in nitric oxide, a vasodilator and inhibitor of platelet
factor for preeclampsia (first pregnancy, age>40 years, pregnan- aggregation [37]. L-arginine, the substrate for the synthesis of
cy interval of >10 years, BMI >35 kg/m2 at first visit, family nitric oxide, has been proposed as playing a role in preventing
history of preeclampsia, and multiple pregnancies) should be preeclampsia. A recent systematic review of randomized con-
advised to take 75 mg of aspirin daily from the 12th week until trolled trials investigated the use of L-arginine for the preven-
delivery [7]. The UK NICE guidelines recommend aspirin tion and treatment of preeclampsia. For women at risk of
75 mg/day over the same period of time for women who have preeclampsia and with established hypertensive disease, L-
at least two moderate risk factors (as listed above) or at least one arginine was associated with reduction in preeclampsia and
high risk factor (as listed above) for preeclampsia. [9]. preterm births when compared with placebo [38].
Calcium supplementation during pregnancy for preventing Future therapeutic targets in preeclampsia include the path-
hypertensive disorders has been suggested in studies to lower ways involved in angiogenesis, attempting to restore the an-
the risk of preeclampsia by approximately half, as well as giogenic balance in the placenta, as well as reducing oxidative
reduce the risk of preterm birth and the rare occurrence of the stress [39, 40]. PARP inhibitors have been shown to prevent
composite outcome: death or serious morbidity [24]. The the development of both endothelial dysfunction and hyper-
women participating in these trials were fed a low-calcium tension [41] in rat models of preeclampsia and may prove to
diet and were supplemented with at least 1 g of calcium daily. have therapeutic value.
The evidence for added calcium in the prevention of hyper- There is evidence of an association between dysregulated
tensive disorders, however, is conflicting [25]. pro-angiogenic factors, hypertension, and podocyte injury.
Some studies have reported an association between vitamin Further examination of the mechanism of podocyte injury
D deficiency and increased risk for preeclampsia [26]. A and detachment may identify novel therapeutic targets [42].
Curr Hypertens Rep (2014) 16:473 Page 5 of 6, 473

New guidelines for the prevention of stroke, specifically in 2. ACOG Committee on Practice Bulletins. ACOG practice bulletin.
Chronic hypertension in pregnancy. Obstet Gynecol. 2001;98(1
women, have been put forward by the American Heart
Association/American Stroke Association (AHA/ASA) [43]. 3. Practice ACoO. Practice bulletin #33: diagnosis and management
Recommendations include the use of prophylactic aspirin and/ of preeclampsia and eclampsia. Obstet Gynecol. 2002;99(1):159
or calcium supplements in women with a history of hyperten- 67.
4. Say L, Chou D, Gemmill A, Tunalp , Moller A-B, Daniels J,
sion to prevent preeclampsia. They also suggest that women
et al. Global causes of maternal death: a WHO systematic analysis.
who have had preeclampsia should undergo postpartum screen- Lancet Glob Health. 2014. These are important recent statistics on
ing for any modifiable cardiovascular risk factors and receive causes of maternal death due to hypertension in pregnancy.
appropriate treatment. Finally, they suggest considering treat- 5. Brown CM, Garovic VD. Drug treatment of hypertension in preg-
nancy. Drugs. 2014;74(3):28396. doi:10.1007/s40265-014-0187-
ment of moderately high blood pressure (150219/100
109 mm Hg), although this may prove controversial [44]. 6. Magee LA, Helewa M, Moutquin JM, von Dadelszen P,
Hypertension Guideline Committee, Society of Obstetricians and
Gynaecologists of Canada. Treatment of the hypertensive disorders
of pregnancy. In: Diagnosis, evaluation, and management of the
Conclusions hypertensive disorders of pregnancy. J Obstet Gynaecol Canada:
JOGC J dObstet Gynecol Can JOGC. 2008;30(3 Suppl 1):S2436.
7. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm
It is estimated that hypertensive disorders in pregnancy ac- M, et al. 2013 ESH/ESC Guidelines for the management of arterial
count for 14 % of all maternal deaths [4]. Over the last hypertension: the Task Force for the management of arterial hyper-
decade, new evidence has emerged with respect to the patho- tension of the European Society of Hypertension (ESH) and of the
physiology of preeclampsia, although this has not yet been European Society of Cardiology (ESC). J Hypertens. 2013;31(7):
1281357. doi:10.1097/01.hjh.0000431740.32696.cc. This
incorporated into the development of therapeutic targets.
provides comprehensive guidelines on the treatment of
There are numerous guidelines and recommendations hypertension in pregnancy.
available to the clinician treating preeclampsia. Management 8. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R,
includes control of blood pressure with antihypertensives, the Germano G, et al. 2007 Guidelines for the Management of Arterial
Hypertension: The Task Force for the Management of Arterial
use of low-dose aspirin for prevention, and magnesium sul-
Hypertension of the European Society of Hypertension (ESH) and
phate when indicated. Delivery remains the only definitive of the European Society of Cardiology (ESC). J Hypertens.
treatment. We would also suggest that management should 2007;25(6):110587. doi:10.1097/HJH.0b013e3281fc975a.
include the continued treatment of women with a remote 9. Excellence NIfHaC. Hypertension in pregnancy: the management
of hypertensive disorders during pregnancy. London: NICE 2010.
history of preeclampsia. We believe that the treatment of
Report No.: Contract No.: CG107.
preeclampsia does not end after pregnancy, or even after the 10. Lowe SA, Brown MA, Dekker GA, Gatt S, McLintock CK,
childbearing years. These women need to be followed in later McMahon LP, et al. Guidelines for the management of hypertensive
life for the development of cardiovascular disease risk, and disorders of pregnancy 2008. Aust N Z J Obstet Gynaecol.
2009;49(3):2426. doi:10.1111/j.1479-828X.2009.01003.x.
advised and treated for any modifiable risk factors.
11. Homer CS, Brown MA, Mangos G, Davis GK. Non-proteinuric
pre-eclampsia: a novel risk indicator in women with gestational
Compliance with Ethics Guidelines hypertension. J Hypertens. 2008;26(2):295302. doi:10.1097/HJH.
12. Pettit F, Brown MA. The management of pre-eclampsia: what we
Conflict of Interest Ecaterina Berzan, Ross Doyle, and Catherine M.
think we know. Eur J Obstet Gynecol Reprod Biol. 2012;160(1):6
Brown each declare that they have no conflict of interest.
12. doi:10.1016/j.ejogrb.2011.09.049.
13. Trogstad L, Magnus P, Stoltenberg C. Pre-eclampsia: risk factors
Human and Animal Rights and Informed Consent This article does and causal models. Best Pract Res Clinical Obstet Gynaecol.
not contain any studies with human or animal subjects performed by any 2011;25(3):32942.
of the authors. 14. Wang A, Rana S, Karumanchi SA. Preeclampsia: the role of angio-
genic factors in its pathogenesis. Physiology. 2009;24:14758. doi:
15. Hertig A, Liere P. New markers in preeclampsia. Clin Chim Acta
References Int J Clin Chem. 2010;411(2122):15915. doi:10.1016/j.cca.
16. Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-
Papers of particular interest, published recently, have been eclampsia. Lancet. 2010;376(9741):63144. doi:10.1016/S0140-
highlighted as: 6736(10)60279-6.
Of importance 17. Cetin I, Huppertz B, Burton G, Cuckle H, Gonen R, Lapaire O,
et al. Pregenesys pre-eclampsia markers consensus meeting: what
Of major importance do we require from markers, risk assessment and model systems to
tailor preventive strategies? Placenta. 2011;32(Suppl):S416. doi:
1. Report of the National High Blood Pressure Education Program 10.1016/j.placenta.2010.11.022.
Working Group on High Blood Pressure in Pregnancy. Am J Obstet 18. American College of Obstetricians and Gynecologists, Task Force
Gynecol. 2000;183(1):S122. on Hypertension in pregnancy. Report of the American College of
473, Page 6 of 6 Curr Hypertens Rep (2014) 16:473

Obstetricians and Gynecologists Task Force on Hypertension in 31. Olsen SF, Osterdal ML, Salvig JD, Weber T, Tabor A, Secher NJ.
Pregnancy. Obstet Gynecol. 2013;122(5):112231. doi:10.1097/01. Duration of pregnancy in relation to fish oil supplementation and
AOG.0000437382.03963.88. This is an important recent statement habitual fish intake: a randomised clinical trial with fish oil. Eur J
from ACOG on hypertension in pregnancy. Clin Nutr. 2007;61(8):97685. doi:10.1038/sj.ejcn.1602609.
19. Podymow T, August P. Antihypertensive drugs in pregnancy. 32. Mostello D, Jen Chang J, Allen J, Luehr L, Shyken J, Leet T.
Semin Nephrol. 2011;31(1):7085. doi:10.1016/j.semnephrol. Recurrent preeclampsia: the effect of weight change between preg-
2010.10.007. This provides a comprehensive review of nancies. Obstet Gynecol. 2010;116(3):66772. doi:10.1097/AOG.
antihypertensives used in pregnancy. 0b013e3181ed74ea.
20. Magee LA. Drugs in pregnancy. Antihypertensives. Best Pract Res 33. Maggard MA, Yermilov I, Li Z, Maglione M, Newberry S, Suttorp
Clin Obstet Gynaecol. 2001;15(6):82745. doi:10.1053/beog.2001. M, et al. Pregnancy and fertility following bariatric surgery: a
0232. systematic review. JAMA J Am Med Assoc. 2008;300(19):2286
21. Duley L, Gulmezoglu AM, Henderson-Smart DJ, Chou D. 96. doi:10.1001/jama.2008.641.
Magnesium sulphate and other anticonvulsants for women with 34. Meher S, Duley L. Rest during pregnancy for preventing pre-
pre-eclampsia. Cochrane Database Syst Rev. 2010;11, CD000025. eclampsia and its complications in women with normal blood
doi:10.1002/14651858.CD000025.pub2. pressure. Cochrane Database Syst Rev. 2006;2, CD005939. doi:
22. Duley L, Henderson-Smart DJ, Walker GJ, Chou D. Magnesium 10.1002/14651858.CD005939.
sulphate versus diazepam for eclampsia. Cochrane Database Syst 35. Meher S, Abalos E, Carroli G. Bed rest with or without
Rev. 2010;12, CD000127. doi:10.1002/14651858.CD000127. hospitalisation for hypertension during pregnancy. Cochrane
pub2. Database Syst Rev. 2005;4, CD003514. doi:10.1002/14651858.
23. Duley L, Henderson-Smart DJ, Meher S, King JF. Antiplatelet CD003514.pub2.
agents for preventing pre-eclampsia and its complications. 36. Duley L, Henderson-Smart D, Meher S. Altered dietary salt for
Cochrane Database Syst Rev. 2007;2, CD004659. doi:10.1002/ preventing pre-eclampsia, and its complications. Cochrane
14651858.CD004659.pub2. Database Syst Rev. 2005;4, CD005548. doi:10.1002/14651858.
24. Hofmeyr GJ, Lawrie TA, Atallah AN, Duley L. Calcium CD005548.
supplementation during pregnancy for preventing hyperten- 37. Meher S, Duley L. Nitric oxide for preventing pre-eclampsia and its
sive disorders and related problems. Cochrane Database Syst complications. Cochrane Database Syst Rev. 2007;2, CD006490.
Rev. 2010;8, CD001059. doi:10.1002/14651858.CD001059. doi:10.1002/14651858.CD006490.
pub3. 38. Dorniak-Wall T, Grivell RM, Dekker GA, Hague W, Dodd JM. The
25. European Society of Gynecology (ESG), Association for European role of L-arginine in the prevention and treatment of pre-eclampsia:
Paediatric Cardiology (AEPC), German Society for Gender a systematic review of randomised trials. J Hum Hypertens.
Medicine (DGesGM), Regitz-Zagrosek V, Blomstrom Lundqvist 2014;28(4):2305. doi:10.1038/jhh.2013.100. This recent paper
C, Borghi C, et al. ESC guidelines on the management of cardio- provides some insight into possible future therapies.
vascular diseases during pregnancy: the Task Force on the 39. Wang K, Ahmad S, Cai M, Rennie J, Fujisawa T, Crispi F, et al.
Management of Cardiovascular Diseases during Pregnancy of the Dysregulation of hydrogen sulfide producing enzyme cystathionine
European Society of Cardiology (ESC). Eur Heart J. 2011;32(24): gamma-lyase contributes to maternal hypertension and placental
314797. doi:10.1093/eurheartj/ehr218. These guidelines provide abnormalities in preeclampsia. Circulation. 2013;127(25):251422.
up-to-date information on the management of cardiovascular dis- doi:10.1161/CIRCULATIONAHA.113.001631.
ease in pregnancy. 40. George EM, Cockrell K, Aranay M, Csongradi E, Stec DE, Granger
26. Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, JP. Induction of heme oxygenase 1 attenuates placental ischemia-
Roberts JM. Maternal vitamin D deficiency increases the risk of induced hypertension. Hypertension. 2011. doi:10.1161/
preeclampsia. J Clin Endocrinol Metab. 2007;92(9):351722. doi: hypertensionaha.111.169755.
10.1210/jc.2007-0718. 41. Walsh SK, English FA, Crocker IP, Johns EJ, Kenny LC.
27. De-Regil LM, Palacios C, Ansary A, Kulier R, Pena-Rosas JP. Contribution of PARP to endothelial dysfunction and hypertension
Vitamin D supplementation for women during pregnancy. in a rat model of pre-eclampsia. Br J Pharmacol. 2012;166(7):
Cochrane Database Syst Rev. 2012;2, CD008873. doi:10.1002/ 210916. doi:10.1111/j.1476-5381.2012.01906.x.
14651858.CD008873.pub2. 42. Craici IM, Wagner SJ, Weissgerber TL, Grande JP, Garovic VD.
28. Roberts JM, Myatt L, Spong CY, Thom EA, Hauth JC, Leveno KJ, Advances in the pathophysiology of pre-eclampsia and related
et al. Vitamins C and E to prevent complications of pregnancy- podocyte injury. Kidney Int. 2014. doi:10.1038/ki.2014.17. This is
associated hypertension. N Engl J Med. 2010;362(14):128291. a comprehensive review of podocyte injury in preeclampsia.
doi:10.1056/NEJMoa0908056. 43. Bushnell C, McCullough LD, Awad IA, Chireau MV, Fedder WN,
29. Sorensen JD, Olsen SF, Pedersen AK, Boris J, Secher NJ, Furie KL, et al. Guidelines for the prevention of stroke in women: a
FitzGerald GA. Effects of fish oil supplementation in the third statement for healthcare professionals from the American Heart
trimester of pregnancy on prostacyclin and thromboxane produc- Association/American Stroke Association. Stroke J Cereb Circ.
tion. Am J Obstet Gynecol. 1993;168(3 Pt 1):91522. 2014;45(5):154588. doi:10.1161/01.str.0000442009.06663.48.
30. Makrides M, Duley L, Olsen SF. Marine oil, and other prostaglan- These recommendations provide important guidance for stroke
din precursor, supplementation for pregnancy uncomplicated by prevention in women with a history of preeclampsia.
pre-eclampsia or intrauterine growth restriction. Cochrane 44. Mitka M. New guidelines focus on preventing stroke in women.
Database Syst Rev. 2006;3, CD003402. doi:10.1002/14651858. JAMA J Am Med Assoc. 2014;311(10):10034. doi:10.1001/jama.
CD003402.pub2. 2014.1775.