REVIEW

CURRENT
OPINION Hypertensive disease of pregnancy and
maternal mortality
Jamie O. Lo, John F. Mission, and Aaron B. Caughey

Purpose of review
The incidence of hypertensive disorders in pregnancy is increasing and is associated with maternal
mortality worldwide. This review provides the obstetrician with an update of the current issues concerning
hypertension and maternal mortality.
Recent findings
Preeclampsia affects about 3% of pregnancies, and all other hypertensive disorders complicate
approximately 510% of pregnancies in the United States. In industrialized countries, rates of
preeclampsia, gestational hypertension, and chronic hypertension have increased as rates of eclampsia
have decreased following widespread antenatal care and magnesium sulfate use. Increased maternal
mortality is associated with eclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome,
hepatic or central nervous system hemorrhage, and vascular insult to the cardiopulmonary or renal system.
Diagnosis and acute management of severe hypertension is central to reducing maternal mortality. African-
American women have a higher risk of mortality from hypertensive disorders of pregnancy compared with
Hispanic, American Indian/Alaska Native, Asian/Pacific Islander, and Caucasian women.
Summary
Hypertensive disorders in pregnancy are a leading cause of maternal mortality worldwide. The incidence
of hypertension in pregnancy continues to increase. Currently, we are unable to determine which patient
will develop superimposed preeclampsia or identify subsets of preeclampsia syndrome. Opportunities for
research in this area exist to better define treatment aimed at improving maternal outcomes.
Keywords
hypertension, mortality, preeclampsia, pregnancy

INTRODUCTION subsequently develop preeclampsia [4]. Preeclamp-

Hypertensive disorders of pregnancy are important
causes of maternal morbidity and mortality world-
wide. Hypertension is one of the most commonly
reported health conditions among pregnant women
and complicates 510% of all pregnancies [1,2].
Along with infection and hemorrhage, it stands
among the three most common causes of maternal
mortality. It has been reported that in the United
States from 1991 to 1997 almost 16% of 3201
maternal deaths were results of pregnancy-related
hypertension complications [3].
During pregnancy, hypertension is categorized
as chronic hypertension, gestational hypertension,
preeclampsia (consisting of mild preeclampsia,
superimposed preeclampsia, and severe preeclamp-
sia), and eclampsia. There is some association
between the groups as women with nonproteinuric
hypertension (i.e. gestational hypertension) are at
risk for developing superimposed preeclampsia, and
about 17% of patients with gestational hypertension
sia is seen at greater rates in nulliparous women and
at the extremes of maternal age in both younger
women and older women. Women aged 35 years or
greater are also at increased risk for chronic hyper-
tension with superimposed preeclampsia. Other risk
factors for preeclampsia include race and ethnicity,
lower socioeconomic status, environment, obesity,
and multiple gestations.
There has been an increasing trend in chronic
hypertension, gestational hypertension, and pree-
clampsia [5]. Hypertensive disorders are associated
with increased rates of maternal mortality and
Department of Obstetrics and Gynecology, Oregon Health & Science
University, Portland, Oregon, USA
Correspondence to Jamie O. Lo, MD, 3181 SW Sam Jackson Park Road,
Mail Code L466, Portland, OR 97239, USA. Tel: +1 503 679 2025; fax:
+1 503 494 4473; e-mail: Loj@ohsu.edu
Curr Opin Obstet Gynecol 2013, 25:124132
DOI:10.1097/GCO.0b013e32835e0ef5

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KEY POINTS

Hypertensive disorders of pregnancy are a major cause
of maternal morbidity and mortality worldwide.

In industrialized countries, rates of preeclampsia,
gestational hypertension, and chronic hypertension have
increased as the rates of eclampsia have decreased.

Increased mortality is associated with eclampsia, HELLP
syndrome, a delay in diagnosis, hemorrhage in the
hepatic or central nervous system, and vascular insult to
the cardiopulmonary or renal system.

The introduction of pregnancy hypertension guidelines
and increased awareness of the importance of blood
pressure reduction (<160/110) have decreased the
incidence of adverse maternal outcomes and mortality.

African-American women have an increased risk of
hypertensive disorders of pregnancy, eclampsia, and
maternal mortality.
morbidity, especially in cases of severe preeclampsia
&
or eclampsia [6 ]. In the United States, the incidence
of eclampsia in 1998 was approximately 1 in 3250
and in the United Kingdom, approximately 1 in
2000 [7,8]. However, the incidence of eclampsia is
declining secondary to improved antenatal care and
use of magnesium sulfate [9,10].
DEFINITION OF MATERNAL MORTALITY
Several governing bodies have defined maternal
mortality.
World Health Organization
The International Classification of Diseases, 10th
edition (ICD-10) defines maternal death as the
death of a woman while pregnant or within 42 days
(or 1 year for late maternal deaths) of termination of
pregnancy, irrespective of the duration and site
of the pregnancy, from any cause related to or
aggravated by the pregnancy or its management,
but not from accidental or incidental causes.
Center for Disease Control and American
College of Obstetrics and Gynecology
A pregnancy-associated death is the death of any
woman, from any cause, while pregnant or within
1 calendar year of termination of pregnancy, regard-
less of the duration and the site of pregnancy.
A pregnancy-related death is a pregnancy-associated
death resulting from complications of the pregnancy
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Hypertension and maternal mortality Lo et al.
itself, the chain of events initiated by the pregnancy
that led to death, or aggravation of an unrelated
condition by the physiologic or pharmacologic
effects of the pregnancy that subsequently caused
death.
DEFINITIONS AND CLASSIFICATIONS OF
HYPERTENSIVE DISORDERS OF
PREGNANCY
There are four major hypertensive disorders related
to pregnancy.
Chronic hypertension
Chronic hypertension is defined as hyperten-
sion (140 mmHg or diastolic blood pressure
90 mmHg) that is diagnosed before pregnancy or
before 20 weeks of gestation. Hypertension that is
first diagnosed after 20 weeks gestation and persists
for greater than 12 weeks postpartum is also
considered chronic hypertension [11].
Gestational hypertension
Gestational hypertension is defined as hyperten-
sion (140 mmHg or diastolic blood pressure
90 mmHg) that develops in pregnancy after
20 weeks gestation and resolves before 12 weeks
postpartum in the absence of proteinuria (<300 mg
of protein in 24 h) [11].
Preeclampsia
Preeclampsia is a syndrome and is typically charac-
terized as new-onset hypertension (140 mmHg
or diastolic blood pressure 90 mmHg) and pro-
teinuria (300 mg of protein in 24 h) diagnosed in
pregnancy often after 20 weeks gestation [11].
Systemic complications of preeclampsia include
renal, hematological, hepatic, neurologic, or pul-
monary function. Preeclampsia can also cause fetal
growth restriction or placental abruption. The find-
ings that make the diagnosis of preeclampsia more
certain are listed below [11].
(1) Diagnostic criteria for severe preeclampsia:
(a) blood pressure of at least 160 mmHg systolic
or at least 110 mmHg diastolic on two
occasions at least 6 h apart;
(b) proteinuria of at least 5 g per 24 h;
(c) platelet counts less than 100 000 cells/ml;
(d) serum transaminase concentration of at
least twice normal;
(e) persistent headache or other cerebral or
visual disturbances;
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 Maternal-fetal medicine
(f) persistent epigastric or right upper quadrant
pain;
(g) oliguria of less than 500 ml in 24 h;
(h) fetal growth restriction;
(i) pulmonary edema or cyanosis;
(2) laboratory findings associated with increased
likelihood of preeclampsia:
(a) increased serum creatinine levels (>1.2 mg/
dl unless previously elevated);
(b) evidence of microangiopathic hemolytic
anemia (with increased lactic-acid dehydro-
genase);
(c) increased uric acid.
Chronic hypertension with superimposed
preeclampsia
Chronic hypertension with superimposed pre-
eclampsia is defined as chronic hypertension in
the setting of new-onset worsening blood pressures,
proteinuria (300 mg of protein in 24 h), thrombo-
cytopenia, or any other systemic features of the
preeclampsia syndrome [11].
HYPERTENSIVE DISORDERS: MORBIDITY
AND MORTALITY
Eclamptic and noneclamptic hypertensive disorders
are associated with high maternal mortality, especi-
ally in developing countries. Of a total of 600 000
annual global maternal deaths, it is estimated that
greater than 70 000 (12%) are secondary to pre-
eclampsia and eclampsia [1215]. A large study in
2007 reviewed 45 960 deliveries over a 20-year
period (19852005) in India and reported a total
of 202 maternal deaths [10]. Of those cases, hyper-
tensive disorders contributed to 62 (31%) maternal
deaths with 50 (24.7%) because of eclampsia [10].
Maternal deaths occurred in 23.9% of all eclamptic
term gestations and 8.9% of all eclamptic preterm
gestations [10]. There is a stronger association with
maternal mortality and patients with preeclamptic
disorders in the setting of hemolysis, elevated liver
enzymes, and low platelet count (HELLP) or partial
HELLP syndrome [10]. In a study of 54 maternal
deaths that occurred among women with HELLP
syndrome, they noted that the events associated
with maternal deaths included hemorrhagic stroke
(45%), cardiopulmonary arrest (40%), disseminated
intravascular coagulopathy (DIC, 39%), adult respir-
atory distress syndrome (28%), renal failure (28%),
hepatic hemorrhage (20%), and hypoxic ischemic
encephalopathy (16%) [16].
Women with preeclampsia and eclampsia have
a 3-fold to 25-fold increased risk of serious com-
plications such as pulmonary edema, abruption,
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aspiration pneumonia, renal failure, hepatic failure,
DIC, and stroke [17]. Hemorrhagic stroke was
reported as the most common cause of death in
patients with eclampsia and resulted in as many
as 60% of all eclampsia-related deaths [18,19].
Another study noted that the most common cause
of mortality in patients with eclamptic disorders was
the presence of pulmonary edema [10]. A recent case
series of 28 women with severe preeclampsia and
eclampsia-related stroke noted a 54% maternal
mortality [19]. There is also an increased frequency
of blood transfusions and need for mechanical
ventilation in preeclamptic and eclamptic patients
compared with normotensive women. Although the
incidence and death from eclampsia has been sig-
nificantly reduced in developed countries, it still
remains a problem in developing countries.
HYPERTENSIVE DISORDERS AND THEIR
RECENT TRENDS IN THE WORLD
In developed countries from 1997 to 2002, the
leading cause of death was hypertension (16.1%)
followed by embolism (14.9%) and hemorrhage
(13.4%) [20] (Fig. 1). A large retrospective study in
the Netherlands in 2009 noted that maternal
mortality increased from 1983 to 2005 and pre-
eclampsia remained the number one direct cause
during the study period [21]. Of those deaths,
cerebral hemorrhage was the leading mode of death
and most cases were associated with high systolic
blood pressure and low platelet counts [21].
The WHO systematically reviews maternal
mortality worldwide and examined 34 datasets
(35 197 maternal deaths) from 1997 to 2002 noting
regional variation in maternal death (Table 1) [20].
Reports from the industrialized countries estimate
that preeclampsia complicates between 3 and 5% of
pregnancies [20]. In Africa, the leading cause of
death is hemorrhage (33.9%) followed by infection
(9.7%) and hypertension (9.1%) [20]. In Asia, the
leading cause of death is hemorrhage (30.8%),
followed by infection (11.6%) and hypertension
(9.1%) [20]. In Latin America and the Caribbean,
the leading cause of death is hypertension (25.7%),
followed by hemorrhage (20.8%) and obstructed
labor (13.4%) [20]. Hypertensive disorders in preg-
nancy are responsible annually for approximately
25 000 maternal deaths in Africa, 22 000 maternal
deaths in Asia, 3800 maternal deaths in Latin
American and the Caribbean, and 150 maternal
&
deaths in industrialized countries [6 ]. Most
maternal deaths are attributable to eclampsia; in
Africa, Asia, Latin America and the Caribbean,
10% of all maternal deaths were caused by eclampsia
[12].
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 Hypertension and maternal mortality Lo et al.

Proportion of maternal 40%

deaths

35%

30%

25%

20% Hemorrhage
Hypertensive disorders
15% Sepsis/infection

10%

5%

0%
Developed Africa Asia Latin America
countries and the
Caribbean

FIGURE 1. Leading causes of maternal mortality worldwide. Data from Khan et al. [20].

Maternal mortality secondary to noneclamptic
hypertensive disorders has increased in incidence
from 3% in 19931997 to 23% in 20012005 [10].
The incidence of eclampsia has been decreasing over
the years, largely because it is somewhat preventable
by adequate prenatal care and therapy for seizure
prophylaxis. For example, there is a decreasing trend
in maternal deaths in India secondary to eclamptic
disorders from 43% in 19851989 to 8.8% in 2001
2005 [10].
HYPERTENSIVE DISORDERS, THEIR
RECENT TRENDS, AND MATERNAL
MORTALITY IN THE UNITED STATES
Over the past two decades, the rate of maternal
chronic hypertension has nearly doubled in the
&
United States [22 ]. The rate of maternal chronic
hypertension increased only by 16% during the
1990s, but increased by 67% from 2000 to 2009,
largely secondary to the obesity epidemic and the
&
increase in maternal age [22 ]. Rates of chronic
hypertension have increased for all racial and
Hispanic ethnicity groups, with the largest increase
among non-Hispanic black women (by 87%) and
&
the lowest among Asian Pacific Islanders [22 ]. The
2011 National Vital Statistic Report reported an
increased incidence of chronic hypertension in all
pregnant women from 11.9 in 2008 to 12.7 per 1000
in 2009. The rates of chronic hypertension were also
noted to increase steadily with age, whereas rates of
gestational hypertension were stable for women
under 40 years but increased sharply after age 40
&
[22 ].
A large cross-sectional study in 2009 noted that
there were linear increasing trends in the United
States significant for all types of hypertensive dis-
orders except for mild preeclampsia [5]. Although
the highest increase was for chronic hypertension,
the study noted that the prevalence of hypertensive
disorders among delivery hospitalizations increased
significantly from 67.2 per 1000 deliveries in 1998
to 81.4 per 1000 deliveries in 2006 [5]. In the
United States, gestational hypertension complicates
roughly 23% of pregnancies and preeclampsia
complicates approximately 3% of pregnancies
[5,9]. When examining the prevalence of hospital-
izations with eclampsia or severe preeclampsia,
there is a moderate increase from 9.4 in 1998 to
12.5 in 2006 per 1000 deliveries [5]. The increasing
trend of chronic hypertension, gestational hyper-
tension, and preeclampsia has likely occurred as a

Table 1. Distribution of causes of maternal mortality worldwide

Developed countries Africa Asia Latin America and the Caribbean

Number of datasets 5 8 11 10
Maternal deaths 2823 4508 16 089 11 777
Hemorrhage 13.4% 33.9% 30.8% 20.8%
Hypertensive disorders 16.1% 9.1% 9.1% 25.7%
Sepsis/infection 2.1% 9.7% 11.6% 7.7%

Data from Khan et al. [20].

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 Maternal-fetal medicine
result of changes in the maternal characteristics (i.e.
&
maternal age and prepregnancy weight) [6 ].
It has been reported that in the United States
from 1991 to 1997, almost 16% of 3201 maternal
deaths were results of pregnancy-related hyperten-
sion complications [3]. In a study of 790 maternal
deaths in the United States from complications of
preeclampsia or eclampsia, 7% were attributed to
hemolysis, elevated liver enzymes, and low platelet
count, while 4% were from abruption [23]. How-
ever, because of improved access to antenatal care,
early delivery of women with severe preeclampsia,
and the utilization of magnesium sulfate, the age-
adjusted frequency of eclampsia has decreased
nonsignificantly from 10.4 per 10 000 deliveries
between 1987 and 1995 to 8.2 per 10 000 deliveries
between 1996 and 2004 in the United States [9].
RACIAL DISPARITIES
A large, 10-year, longitudinal, population-based
study in New York State from 1993 to 2002 studied
trends of hypertensive disorders of pregnancy by
racial and ethnic subgroups (Table 2). Among non-
diabetics, they found higher rates of preeclampsia
among African-American women and Hispanic
women than among Caucasian women regardless
of neighborhood poverty level [24]. This racial dis-
parity was noted to increase over the decade.
Smaller, but substantial, differences between hyper-
tension rates of Hispanic and Caucasian women
were identified over time in New York State [24].
A review in 2010 examined the existing literature
regarding racial and ethnic disparities in obstetrics
outcomes among African-American, Hispanic,
American Indian/Alaska Native, and Asian/Pacific
Islander women [25]. The review reported that
African-American women were more likely to
experience hypertensive disorders of pregnancy,
some of which may be attributable to excess cases
of prepregnancy hypertension [24,26,27]. Among
Asian women, the study noted that Filipina and
Table 2. Rates of hypertensive disorders during pregnancy among different racial/ethnic groups
Chronic
Incidence n hypertension
White 1 297 460 1.1
Hispanic 310 858 0.9
African American 450 098 2.1
Other 512 653 1.1
Data from Tanaka et al. [24], New York State, 19932002. Rate # of events/100 hospitalizations with delivery.
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Samoan women have risks higher than women from
other subgroups [2830]. There is evidence that Asian
paternity is associated with a reduction in pre-
eclampsia risk and racial/ethnic discordance between
parents associated with a small increased risk [31].
In 2005, maternal mortality rates for Caucasian
women were 11.7 per 100 000 live births, 9.6 for
Hispanic women, and 39.2 for non-Hispanic black
women [32]. A study from 2007 examined the
prevalence and case-fatality rates among African-
American and Caucasian women for preeclampsia,
eclampsia, abruptio placentae, placenta previa, and
postpartum hemorrhage using national datasets
from 1988 to 1999 [33]. This study concluded that
African-American women did not have significantly
greater prevalence rates than Caucasian women, but
African-American women with these conditions
were 23 times more likely to die from them than
Caucasian women [33]. African-American women
also have an increased risk of severe complications
including need for mechanical ventilation and
blood transfusion and are 3.1 times more likely to
die from preeclampsia or eclampsia compared with
Caucasian women [17,23]. Currently, few data
exist regarding the racial differences in biological
mediators of preeclampsia. To better explain dis-
parities in hypertensive disorders, further studies
in these areas are needed.
EMERGENT THERAPY FOR ACUTE-ONSET,
SEVERE HYPERTENSION WITH
PREECLAMPSIA OR ECLAMPSIA
It is a hypertensive emergency when a pregnant or
postpartum woman with preeclampsia or eclampsia
has acute-onset, sustained (15 min), severe hyper-
tension (160 mmHg systolic or 110 mmHg dias-
tolic). Severe systolic hypertension is the most
important predictor of cerebral hemorrhage and
infarction in these patients and often a key factor
&& &&
in maternal deaths from aortic dissection [34 ,35 ].
If not treated expeditiously, it can result in
Severe
Gestational Superimposed preeclampsia
hypertension Preeclampsia preeclampsia and eclampsia Total
1.8 2.0 0.2 0.7 5.5
1.2 3.0 0.3 1.0 6.2
1.5 3.3 0.7 1.2 8.5
1.2 2.3 0.3 0.9 5.5
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complications such as cerebral hemorrhage and
maternal death. Thus, morbidity and mortality risk
reduction for women with preeclampsia or eclamp-
sia requires management and avoidance of severe
&&
systolic and diastolic hypertension [35 ]. The intro-
duction of guidelines in the United States for the
management of patients with preeclampsia and
eclampsia and increased awareness of the import-
ance of blood pressure reduction has been associated
with a decrease in the incidence of adverse maternal
outcomes [36,37]. Similarly, in the United Kingdom,
the advent of pregnancy hypertension guidelines
was associated with significantly improved care of
preeclampsia and eclampsia patients and decreased
maternal mortality presumptively because of a
reduction in cerebral and respiratory complications
&&
[34 ,38].
Acute hypertension
The goal of antihypertensive therapy is not to
normalize blood pressures, but to achieve a range
of 140159/90100 mmHg to prevent prolonged
exposure to severe systolic hypertension, with sub-
sequent loss of cerebral vasculature autoregulation
&&
[35 ]. Acute first-line therapy includes both labeta-
&&
lol and hydralazine (Table 3) [11,35 ]. Intravenous
labetalol is recommended as it is effective and gener-
ally well tolerated in pregnancy. Guideline recom-
mendations are to begin with 20 mg intravenously
followed at 10-min intervals by doses of 40 mg, then
&&
80 mg, then 80 mg for a total of 220 mg [11,35 ]. A
fall in blood pressure within 510 min is expected. If
desired blood pressure levels are not achieved,
switch to another drug. Intravenous hydralazine is
also recommended, although a meta-analysis has
demonstrated a slight increase in adverse events
compared with labetalol, but without sufficient
data to recommend one drug over the other [39].
Hydralazine dosing begins with 5 mg intravenously
or 10 mg intramuscularly followed at 20-min
intervals by a 510 mg bolus depending upon
the initial response. A drop in blood pressure within
1030 min is expected. Once the blood pressure
Table 3. Treatment for acute hypertension
Drug Dose
Labetalol 20 mg i.v. then 4080 mg every 10 min
for total of 220 mg
Hydralazine 5 mg i.v. or 10 mg i.m. then 510 mg every
20 min for total of 20 mg i.v. or 30 mg i.m.
Nifedipine 10 mg p.o. then every 30 min up to five doses
&&
Data from Refs. [11,35 ].
i.m., intramuscular; i.v., intravenous.
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Hypertension and maternal mortality Lo et al.
control has been achieved, repeat as needed (usually
about 3 h). If there is no success with a total of
20 mg intravenously or 30 mg intramuscularly,
consider using another antihypertensive medi-
&&
cation [11,35 ]. Infrequently, both intravenous
labetalol and hydralazine will fail to resolve acute-
onset, severe hypertension when given in successive
appropriate doses as those outlined in Table 3. In
this rare circumstance, emergent consultation with
an anesthesiologist, maternalfetal medicine sub-
specialist, or critical care specialist to discuss second-
&&
line intervention is recommended [35 ]. Second-
line therapy includes continuous intravenous
&&
labetalol or nicardipine [35 ]. Less information
exists for the use of calcium channel blockers for
this clinical situation, but oral nifedipine can also be
used: start with 10 mg orally and repeat every 30 min
&&
if necessary up to five doses [11,40 ]. A recent,
double-blind, randomized controlled trial demon-
strated similar effectiveness with oral nifedipine and
intravenous labetalol regimens in the acute control
&&
of severe hypertension [40 ].
Treatment and prevention of eclampsia
Different therapies to prevent eclamptic convul-
sions in the setting of preeclampsia have been well
studied. However, magnesium sulfate remains the
drug of choice for seizure prophylaxis in severe
preeclampsia and for controlling seizures in eclamp-
sia (Table 4). The Magpie Trial in 2002 was a
randomized, placebo-controlled trial that compared
intravenous magnesium sulfate with placebo [41].
The study enrolled 10 141 women with preeclamp-
sia (BP 140/90, 1 proteinuria) and found that
magnesium sulfate given as a 4-g intravenous load
and 1 g/h maintenance dose significantly reduced
the risk of eclampsia by half, thus reducing the risk
of maternal death. A randomized controlled trial
conducted in 2003 on 1650 women compared
magnesium sulfate and nimodipine for seizure
prophylaxis in women with severe preeclampsia
[42]. They concluded that magnesium sulfate was
more effective than nimodipine (2.6 versus 0.8%,
Concerns or Comments
May increase the risk of neonatal bradycardia
May increase risk of maternal hypotension
Tachycardia, palpitations, and headache
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 Maternal-fetal medicine
Table 4. Randomized controlled trials of magnesium sulfate prophylaxis versus placebo or active drug
Seizures/total (%)
Study Magnesium
Magpie Trial [41] preeclampsia 40/5055 (0.8)
Belfort et al. [42] severe preeclampsia 7/831 (0.8)
Lucas et al. [43] all hypertensives 0/1049 (0)
RR, relative risk.
P 0.01) for seizure prophylaxis. A randomized con-
trolled trial in 2005 of 2138 women compared
phenytoin and magnesium sulfate for the preven-
tion of eclamptic convulsions in pregnant women
with hypertension [43]. The results noted that 10 of
1089 women randomly assigned to phenytoin had
eclamptic convulsions compared to none of 1049
women randomly assigned to magnesium. The
study concluded that magnesium sulfate was
superior to phenytoin when given prophylactically
for eclamptic seizures to women with peripartum
hypertension [43]. A Cochrane review in 2010
reviewed 15 trials comparing magnesium sulfate
and other anticonvulsants for women with pre-
eclampsia [44]. The meta-analysis concluded that
magnesium sulfate was superior to placebo, pheny-
toin, and nimodipine and more than halves the risk
of eclampsia (Table 4). Of note, some providers
utilize a higher magnesium dosing regimen (6 g
intravenous load and 2 g/h maintenance dose),
but no studies have demonstrated that this regimen
leads to a greater reduction in seizures than the
41 g/h dosing used in the Magpie Trial. Thus,
we recommend the 41 g/h dosing to reduce the
side-effects and complications from magnesium
toxicity.
LONG-TERM OUTCOMES
Although maternal mortality from hypertensive
disease in pregnancy is less common in developed
countries, there are severe morbidities (e.g. chronic
hypertension and chronic renal disease) associated
with preeclampsia and eclampsia that can lead to
long-term mortality. Women with hypertensive dis-
ease in pregnancy should be counseled regarding
the possible long-term risks including increased
cardiovascular morbidity, cerebrovascular disease,
renal, and neurological sequelae. Most pregnancy-
related hypertension resolves within 12 weeks
postpartum, but the longer hypertension persists
postpartum, the greater the likelihood that the
woman has chronic hypertension. In 2007, the
MAGPIE Trial Follow-up Collaborative Group noted
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Control Comparison
Placebo 96/5055 (1.9) RR 0.42 (0.260.60)
Nimodipine 21/819 (2.6) RR 0.33 (0.140.77)
Phenytoin 10/1089 (0.9) P < 0.001
that 20% of 3375 preeclamptic women when eval-
uated at a median of 26 months postpartum had
hypertension [45]. An earlier gestational age of pre-
eclampsia onset and delivery in the first pregnancy
is associated with an increased risk of recurrent
preeclampsia in a subsequent pregnancy. In 2009,
a study in Finland examined 536 419 Finnish
women whose first pregnancy was complicated
by preeclampsia and delivered between 32 and
36 weeks [46]. Women experienced a significantly
increased incidence of preeclampsia in their second
pregnancy (25 versus 14%) compared with those
who delivered after 37 weeks. A different study from
Finland of 896 women reported that depending
on the diagnosis in the initial pregnancy, there is
a 5894% recurrence risk of some type of hyper-
tensive disorder in the second pregnancy [47].
In 2007, a large systematic review and meta-
analysis of the long-term risks for cardiovascular
disease in women with preeclampsia noted a
statistically significant increased risk of hyperten-
sion, ischemic heart disease, stroke, and venous
thromboembolism [48]. The relative risks (RR)
[95% confidence interval (CI)] for hypertension
were 3.70 (2.705.05) after 14.1 years weighted
mean follow-up, for ischemic heart disease 2.16
(1.862.52) after 11.7 years, for stroke 1.81 (1.45
2.27) after 10.4 years, and for venous thromboemb-
olism 1.79 (1.372.33) after 4.7 years. Overall,
mortality after preeclampsia was increased with a
RR of 1.49 (1.052.14) after 14.5 years. Another
large systematic review and meta-analysis in 2008
evaluated 15 casecontrol and cohort studies and
noted that relative to women with uncomplicated
pregnancies, women with a history of preeclampsia
and eclampsia had approximately double the risk of
subsequent cardiac disease, cerebrovascular disease,
peripheral arterial disease, and cardiovascular
mortality [49]. The same study also reported a
graded relationship between the severity of pre-
eclampsia and eclampsia and the risk of cardiac
disease [49].
Previously, eclamptic seizures were thought to
not have significant long-term sequelae, but more
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April 2013

recent casecontrol studies have noted long-term
persistence of brain white matter lesions incurred at
& Papers of particular interest, published within the annual period of review, have
the time of eclamptic convulsions [50,51 ]. Using
magnetic resonance imaging, these studies noted an
increased incidence of cerebral white matter lesions
&
and severity compared with controls [50,51 ]. At a
mean of 7.1 years, one study noted 40% of pre-
viously eclamptic women had larger aggregate white
matter lesions compared with 17% of controls, but
no clinical relevance was established. However, a
more recent casecontrol study in 2012 conducted
in the Netherlands noted that formerly eclamptic
women express lower vision-related quality of life
than controls in part because of the presence of
& 6. Hutcheon JA, Lisonkova S, Joseph KS. Epidemiology of preeclampsia and the
white matter lesions [52 ].
Women with a history of preeclampsia are also
at an increased risk of developing renal disease. A
large, 40-year, retrospective study noted that
although the absolute risk of renal failure in women
with a history of preeclampsia is low, preeclampsia is
a marker for a four-fold increased risk of subsequent
end-stage renal disease [53].
CONCLUSION
Hypertensive disorders in pregnancy remain the
leading causes of maternal mortality worldwide,
and one of the keys to reducing mortality is in
controlling blood pressures in the severe range
(160/110). The incidence of hypertension in preg-
nancy continues to increase, and we are currently
unable to determine which patient will develop
superimposed preeclampsia. Preeclampsia affects
about 3% of pregnancies, and all other hypertensive
disorders complicate approximately 510% of preg-
nancies in the United States. Maternal mortality
from hypertensive disorders is largely associated
with stroke; however, contributing factors other
than systemic blood pressure alone are poorly
understood and further investigation is needed to
define the patient at risk of stroke. There are oppor-
tunities for new research in this area to better define
treatment strategies aimed at improving maternal
and fetal outcomes. Further research is also necess-
ary to study and better understand the heterogen-
eity in outcomes and risk factors for all types of
hypertensive disorders.
Acknowledgements
None.
Conflicts of interest
The authors have no conflict of interest to declare with
respect to any of the content of this article.
Funding: None.
1040-872X 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Hypertension and maternal mortality Lo et al.
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Volume 25
Number 2
April 2013