Preeclampsia

Short-term and Long-term Implications

Jaimey M. Pauli, MD*, John T. Repke, MD

KEYWORDS
 Preeclampsia  Hypertension  Pregnancy  Prenatal screening
 Cardiovascular risk

KEY POINTS
 Preeclampsia is a hypertensive disease specific to pregnancy with a high risk of maternal
and fetal morbidity and mortality, as well as long-term cardiovascular risks to both the pa-
tient and her child.
 The cause of preeclampsia is not fully understood, but is most likely to be abnormal
placentation and release of placental factors that contribute to systemic endothelial
function.
 Risk factor and biochemical/biophysical screening tests are available to approximate the
risk of developing preeclampsia. Low-dose aspirin may reduce the risk of preeclampsia in
high-risk patients; however, the ultimate cure remains delivery of the fetus and placenta.
 Diagnosis of preeclampsia is defined by hypertension with either proteinuria or signs of
severe multiorgan dysfunction.
 Management of preeclampsia depends on gestational age at diagnosis and the presence
of severe symptoms, and involves continuous maternal and fetal evaluation for worsening
of disease prompting delivery. Postpartum hypertension and preeclampsia require vigi-
lance on the part of both the medical provider and the patient to reduce morbidity.

Preeclampsia affects approximately 4% of all pregnancies1,2 and is a major cause of

maternal, fetal, and neonatal morbidity and mortality worldwide. It is a unique disease
in several ways: it is one of only a small number of pathologic conditions that are spe-
cific to pregnancy; it is, by definition, a precursor of a potentially severe disease
(eclampsia) but is lethal in its own right; it has had the same essential treatment (de-
livery) for hundreds of years; and its fundamental cause and prevention continue to
elude researchers. It has recently become topical, both in mainstream and medical
communities, at least in part because of its increasing incidence (25% increase in

Disclosures: None.
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Penn State
Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA
* Corresponding author. 500 University Drive, H103, Hershey, PA 17033.
E-mail address: jpauli@[Link]

Obstet Gynecol Clin N Am 42 (2015) 299–313

[Link] [Link]
0889-8545/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
300 Pauli & Repke

the United States in the last 20 years3,4) and severity of disease as it relates to the
obesity epidemic currently facing the world.

DEFINITION

Preeclampsia is a hypertensive disease that is exclusive to pregnancy. It was tradition-

ally defined as the triad of hypertension, proteinuria, and edema occurring after 20 to
24 weeks’ gestation.5 This definition has changed and been refined over the years as
its pathology has been unraveled. Increase in systolic blood pressure of 30 mm Hg or
diastolic blood pressure of 15 mm Hg is no longer part of the definition because these
criteria are not predictive of adverse outcomes. Edema has also been removed from
the definition, because it is too common a clinical finding during pregnancy to be clin-
ically relevant.
It is now defined as new-onset hypertension (systolic blood pressure 140 mm Hg
or diastolic blood pressure 90 mm Hg) and new-onset proteinuria after 20 weeks’
gestation in a previously normotensive patient.4 The hypertension should be docu-
mented to be persistent over 2 determinations at least 4 hours apart, unless it is
greater than or equal to 160 mm Hg systolic or greater than or equal to 110 mm Hg
diastolic. This severe increase may be confirmed in a shorter interval for prompt ther-
apy. Proteinuria is defined as 300 mg of protein in 24 hours or a urine protein/creatinine
ratio of 0.3 mg/dL. Urine dipstick of 11 is only to be used if the other methods are not
available.
In the absence of proteinuria, preeclampsia may also be defined as new-onset hy-
pertension with other signs of multisystem involvement (thrombocytopenia, liver
dysfunction, renal insufficiency, pulmonary edema, cerebral or visual disturbances)
(Table 1).
Preeclampsia is further divided into 2 categories: with and without severe features
(Box 1).
Preeclampsia is part of a collection of hypertensive disorders of pregnancy,
including gestational hypertension, chronic hypertension, and chronic hypertension
with superimposed preeclampsia. Eclampsia (seizure associated with preeclampsia)
and the HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome are

Table 1
Definitions of preeclampsia

Hypertension Proteinuria Multisystem Involvement

140 mm Hg systolic or 300 mg in 24 h Thrombocytopenia
90 mm Hg diastolic
Previously normotensive patient Protein/creatinine ratio Renal insufficiency
>20 wk gestation 0.3 mg/dL
BP measured two times at least Dipstick 11 (only if other Liver dysfunction
4 hours aparta methods not available)
Pulmonary edema
Cerebral or visual disturbances

Abbreviation: BP, blood pressure.

a
Greater than or equal to 160 mm Hg or greater than or equal to 110 mm Hg diastolic may be
confirmed within minutes to facilitate treatment.
Adapted from American College of Obstetricians and Gynecologists, Task Force on Hypertension
in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and
Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013;122(5):1122–31.
 Preeclampsia 301

Box 1
Severe features of preeclampsia

Systolic blood pressure greater than or equal to 160 mm Hg or diastolic blood pressure greater
than or equal to 110 mm Hg on 2 occasions at least 4 hours apart while the patient is on bed rest
Thrombocytopenia (<100,000 platelets/mL)
Impaired liver function (liver enzymes levels increased to twice normal) or persistent right
upper quadrant/epigastric pain unresponsive to medication and not accounted for by a
different diagnosis)
Progressive renal insufficiency (serum creatinine >1.1 mg/dL or doubling of creatinine level
without other renal disease)
Pulmonary edema
Cerebral or visual disturbances

Adapted from American College of Obstetricians and Gynecologists, Task Force on Hyperten-
sion in Pregnancy. Hypertension in pregnancy. Report of the American college of obstetricians
and gynecologists’ task force on hypertension in pregnancy. Obstet Gynecol 2013;122(5):
1122–31.

considered related disorders that may occur without or before the onset of docu-
mented hypertension.
Early-onset preeclampsia is defined as development before 34 weeks’ gestation,
and it affects up to 1% of pregnancies.6 Compared with late-onset disease, early-
onset disease is associated with increased risk of complications, especially early fetal
growth restriction, intensive care, preterm delivery, and a 20-fold increased risk of
maternal mortality.6–8

EPIDEMIOLOGY

Two-thirds of preeclampsia cases occur in otherwise healthy, nulliparous women, so

there is no single most important recognizable risk factor.1 However, there is a classic
list of conditions that predispose a patient to preeclampsia (Table 2).9,10
One-third of cases in the United States are associated with obesity.1 Studies have
shown a progressive increase in risk of preeclampsia as body mass index (BMI) in-
creases. O’Brien and colleagues11 reported a doubling of preeclampsia risk for every
increase of 5 to 7 kg/m2 in prepregnancy BMI. Racial differences in rates of pre-
eclampsia may to be more related to coexisting medical conditions such as hyperten-
sion. Other risk factors include unexplained fetal growth restriction, prior fetal growth
restriction, prior fetal demise, molar pregnancy, and paternal contribution (although
the last factor is controversial).9–12

PATHOPHYSIOLOGY

History has afforded many theories as to the cause of preeclampsia.5 In ancient times,
an imbalance of fluids, or humors, was thought to be linked to disease. Women were
said to be porous and therefore prone to having too much fluid. The so-called wander-
ing womb was thought to uproot itself and therefore cause problems wherever it
landed (ie, the liver, spleen, or lungs). Restoring balance with lactation, menstruation,
or bloodletting was the treatment of choice.
Although not formally defined in ancient times, the writings of Hippocrates have the
likely first reference to eclampsia as convulsions and headache associated with
302 Pauli & Repke

Table 2
Risk factors for preeclampsia

Relative Risk9 Risk10

Nulliparity 3 —
Prior preeclampsia 7 —
Advanced maternal age 2 10%–40% (age >40 y)
Chronic hypertension — 15%–40%
Chronic renal disease — 15%–40%
Diabetes 3.5 10%–35%
Obesity — 10%–15%
Multiple gestation 3 —
Vascular/connective tissue disorder (eg, lupus) — 10%–20%
Antiphospholipid antibody syndrome/thrombophilia 9 10%–40%
Family history of preeclampsia 2–4 10%–15%
Patient born SGA — 1.5-fold
Prior adverse pregnancy outcomes — 2-fold to 3-fold

Abbreviation: SGA, small for gestational age.

Data from Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: system-
atic review of controlled studies. BMJ 2005;330(7491):565; and Barton J, Sibai B. Prediction and pre-
vention of recurrent preeclampsia. Obstet Gynecol 2008;112(2):359–72.

pregnancy. Epilepsy was divided into 4 causative categories in the 1500s, one of
which was the uterus. Eclampsia was defined in the early 1600s. The Frenchman Fran-
cois Mauriceau more extensively studied this disease, noting the increased risk in pri-
migravidas, and again attributing the disease to an imbalance of humors via abnormal
lochial flow or fetal death. Theories of the 1800s included cerebral congestion and
toxic elements (toxemia), leading to more bloodletting and purging. The late 1800s
recognized the connection between hypertension, edema, headache, and proteinuria
as premonitory signs of the convulsions (ie, preeclampsia).
The twentieth century brought both good (placental disorder via abnormal spiral ar-
tery development)13 and bad (the Hydatoxi lualba worm)14 theories. The theory of
endothelial dysfunction at the level of the placenta leading to toxin release and subse-
quent maternal disease was also introduced (Fig. 1).
At present, the most accepted theory of the pathologic cause of preeclampsia is
abnormal placental development as a result of abnormal spiral artery remodeling
and defective trophoblast invasion/differentiation. This process subsequently leads
to a hypoperfusion/hypoxemia/ischemia sequence that causes a release of cytokines
such as soluble fms-like tyrosine kinase-1 (sFlt-1) and vascular endothelial growth fac-
tor (VEGF) that induce systemic endothelial dysfunction and the systemic effects of
the disease. Another corollary theory is that other immunologic factors (human leuko-
cyte antigen [HLA] class 1 antigens, natural killer cells, antibodies to angiotensin AT 1
receptor) may play a role, supported by higher risk of preeclampsia in nulliparous pa-
tients, those who change partner, or those who have long interpregnancy
intervals.15,16

SCREENING

Ideally, there would be a simple, accurate, low-cost test to predict who will develop
preeclampsia so that an effective intervention can be initiated to improve maternal
 Preeclampsia 303

Fig. 1. Historical perspective on the pathophysiology of preeclampsia. VEGF, vascular endo-

thelial growth factor.

and fetal/neonatal outcomes. Such a test has become something of a holy grail in ob-
stetric research. However, all the screening tests in the world do not change the fact
that the only proven intervention remains delivery. Proponents of the screening test
suggest that improved antepartum surveillance, administration of antenatal steroids,
and aspirin therapy are effective interventions that may alter outcomes, but knowing
that a patient has an increased risk of preeclampsia in the first trimester may not
fundamentally change management if the patient does develop preeclampsia.
Risk factor–based screening (see Table 2) is an appropriate evaluation tool when
performing preconception counseling because identification of modifiable risk factors
(eg, obesity) can lead to preconception intervention. Examples of this may be signifi-
cant weight loss and optimization of diabetic control. This screening tool only carries a
29% to 37% detection rate, with a false-positive rate of 5% to 10%.12,17 In addition,
the risk is also related to the severity and duration of certain risk factors, such as
hypertension.10
First trimester uterine artery Doppler velocimetry (flow wave velocity and notching)
has been studied as a potential predictor of adverse perinatal outcomes, particularly
preeclampsia. In a meta-analysis of more than 55,000 mostly low-risk women,
abnormal flow wave velocity was specific (92%) but not sensitive (47%) for predicting
early-onset preeclampsia.6 Abnormal Doppler studies in these low-risk women
increased the risk of early-onset preeclampsia from 0.4% to up to 6%. The investiga-
tors argued that initiation of low-dose aspirin therapy in this patient population has a
number needed to treat of 173 to prevent 1 case of early-onset preeclampsia.6
Another meta-analysis showed that increased pulsatility index with notching of the
uterine artery Doppler in the second trimester best predicted overall preeclampsia
in both low-risk and high-risk patients. Increased pulsatility index or bilateral notching
best predicted the development of severe preeclampsia.18
Audibert and colleagues19 studied combining maternal characteristics (gestational
age, BMI, maternal age) with serum markers and uterine artery Doppler to develop
a prediction model for preeclampsia in nulliparous women. In the first trimester, low
304 Pauli & Repke

levels of pregnancy-associated plasma protein A (PAPP-A), PIGF, and increased

levels of inhibin A were all associated with increased risk of early and severe pre-
eclampsia, with a sensitivity of 75% and false-positive rate of 10% when combined
with clinical characteristics. This study did not find added benefit from first-trimester
uterine artery Doppler studies. Other studies have failed to show a clinically relevant
screening tool using multiple markers in the first trimester.20
Biochemical markers that have been studied for the prediction of preeclampsia are
listed in Box 2. Although preeclampsia has been associated with decreased levels of
angiogenic factors such as placental growth factor (PlGF) and increased levels of anti-
angiogenic factors such as sFlt-1, their use as a screening tool to predict preeclamp-
sia has not been proved.15 Many other biomarkers secreted by the placenta, such as
VEGF, PAPP-A, alpha fetoprotein, inhibin A, and A disintegrin and metalloprotease 12
(ADAM12) have been studied as predictors of preeclampsia in the first and second tri-
mesters. The studies are mostly small and the clinical efficacy as a screening tool has
not been established.21
Cell-free fetal DNA (cffDNA), a product of normal placental apoptosis, has also been
evaluated as a screening tool for preeclampsia. Increased levels of cffDNA are noted
in patients before the onset of symptoms of preeclampsia, purportedly from increased
apoptosis related to placental hypoxia. To date, the clinical relevance of these levels
as a predictive tool is promising but has not been adequately evaluated.22

DIAGNOSIS

Preeclampsia is diagnosed by new-onset hypertension (140 mm Hg systolic or 90

mm Hg diastolic) with proteinuria after 20 weeks’ gestation in a previously normoten-
sive woman. Guidelines for accurate diagnosis include:
 Appropriate maternal positioning for blood pressure assessment (seated, resting
for 5 minutes, legs not crossed, not talking)

Box 2
Potential biochemical/biophysical screening tools for preeclampsia

sFlt-1 [
PAPP-A Y
Placental growth factor (PlGF)
VEGF [
Alpha fetoprotein (AFP) [
Inhibin A [
A disintegrin and metalloprotease 12 (ADAM12) [
Soluble endoglin [
Asymmetric dimethylarginine [
Serum placental protein 13 Y
Cell-free fetal DNA (cffDNA) [
Uterine artery velocimetry (flow wave velocity, notching)

Data from Barton J, Sibai B. Prediction and prevention of recurrent preeclampsia. Obstet
Gynecol 2008;112(2):359–72; and Goetzinger KR, Odibo AO. Screening for abnormal placenta-
tion and adverse pregnancy outcomes with maternal serum biomarkers in the second trimester.
Prenat Diagn 2014;34:635–41.
 Preeclampsia 305

 Persistence of the increased blood pressure (it is recommended that a single

increased measurement be repeated to confirm that it is not isolated)
In 2013, the American College of Obstetricians and Gynecologists (ACOG) released
new guidelines for hypertension in pregnancy4 with the following updates in diagnostic
criteria for preeclampsia:
 Mild preeclampsia is redefined as “preeclampsia without severe features.”
 Severe preeclampsia is redefined as “preeclampsia with severe features.”
 Proteinuria of greater than 5 g has been eliminated from the list of features
defining severe disease.
 This is because of lack of evidence that quantity of protein is associated with a
significant change in outcomes.
 Fetal growth restriction has been removed from the list of features defining se-
vere disease.
 The guidelines state that management of fetal growth restriction is the same
regardless of diagnosis of preeclampsia.
 Again, in the absence of proteinuria, certain features still qualify a patient for
the diagnosis of preeclampsia. These severe features are listed in Box 1.
Women with chronic hypertension have up to a 40% risk of developing superim-
posed preeclampsia.4,23,24 This condition is generally defined as new-onset protein-
uria, sudden escalation in blood pressure that was previously well controlled, or the
appearance of severe symptoms (see Box 1).

MANAGEMENT

The ultimate management of preeclampsia (delivery) is primarily determined by 2

things: gestational age and the presence of severe features.4 For patients who are
term (37 weeks’ gestation) at diagnosis, the recommendation is delivery. For pa-
tients with severe features, the recommendation is delivery if greater than or equal
to 34 weeks’ gestation. Expectant management is appropriate for certain patients if
the patient is willing to undergo the risks of staying pregnant.
Expectant Management of Preeclampsia Without Severe Features
Expectant management of preeclampsia without severe features is summarized in
Fig. 2. It involves close maternal and fetal monitoring with serum laboratory testing,
fetal growth and well-being assessment, and surveillance for development of severe
features. This management may occur as either an outpatient or inpatient depending
on the patient’s clinical status and reliability. Patients should be hospitalized and de-
livery considered if there is the development of any severe features, severe blood
pressure increase, or abnormal fetal testing. Delivery should be effected if 37 weeks’
gestation is attained, labor occurs, or there is persistent abnormal fetal testing or se-
vere fetal growth restriction. Current evidence does not recommend strict bed rest,
antihypertensive therapy for mild to moderate hypertension, or universal magnesium
prophylaxis, because benefit has not been shown for these measures.
Expectant Management of Suspected Preeclampsia with Severe Features at less than
34 Weeks
Expectant management of suspected preeclampsia with severe features at less than
34 weeks is summarized in Fig. 3. Initial evaluation and stabilization should occur in
the hospital. Continuous fetal monitoring, administration of antenatal steroids, and
magnesium sulfate administration for seizure prophylaxis should occur during the
 306
Pauli & Repke
•Maternal serum tesng (liver funcon, renal funcon, CBC with platelets) at diagnosis and weekly
•Fetal growth assessment via ultrasound at diagnosis and then serially every 3 weeks
Outpaent or •Fetal tesng (non-stress tests or biophysical profiles) 2x/week
•Maternal blood pressure assessment 2x/week
Inpaent •Amnioc fluid assessment weekly
•Daily maternal assessment of fetal movement and development of severe features

•Development of any severe features

Indicaons for •Blood pressure ≥ 160 mm Hg systolic or 110 mm Hg diastolic
•Fetal growth restricon
Hospitalizaon •Abnormal fetal tesng

•37 weeks gestaon

•Labor or preterm rupture of membranes
•Development of severe features
Indicaons for •Placental abrupon
•Oligohydramnios
Delivery •Esmated fetal weight < 5th percenle
•Non-reassuring fetal tesng (ex. persistent biophysical profile of ≤ 6/10)
•Paent not willing to connue expectant management

•Strict bedrest
Not •Anhypertensive therapy for blood pressure < 160 mm Hg systolic or < 110 mm Hg diastolic
•Universal magnesium prophylaxis
Recommended •Salt restricted diet
•Expectant management beyond 37 weeks gestaon

Fig. 2. Expectant management of preeclampsia without severe features. CBC, complete blood count.
 • Hospitalizaon and observaon on labor and delivery for 24-48 hours or transfer to facility with appropriate level of maternal/neonatal care
• Connuous fetal monitoring

Inial evaluaon and • Corcosteroids for fetal lung maturity

• Anhypertensive therapy for persistent bp ≥ 160 mm Hg systolic or 110 mm Hg diastolic (see Table 3)
• Serial maternal serum tesng (liver funcon, renal funcon, CBC with platelets) and 24 hour urine protein assessment
stabilizaon • Magnesium sulfate prophylaxis
• Fetal growth assessment via ultrasound
• Serial blood pressure and urine output monitoring

• Eclampsia
Contraindicaons to • Disseminated intravascular coagulaon
• Intrauterine fetal demise
expectant management • Pre-viable gestaon
• Placental abrupon
• Uncontrollable severe hypertension
• Pulmonary edema
(Stabilize paent and deliver) • Non-reassuring fetal heart tracing

Short-term expectant management • ≤ 33 6/7 weeks gestaon

may be appropriate • HELLP syndrome (or any poron of it)
• Fetal growth restricon (<5 percenle)
• Oligohydramnios
(Connuous fetal and maternal • Reversed end diastolic flow of UA Doppler studies
• Labor or preterm rupture of membranes
monitoring, corcosteroids, then • Significant renal dysfuncon
• Persistent severe features
deliver aer 48 hours)

• Daily fetal tesng (non-stress tests, biophysical profiles)

Connued inpaent expectant • Serial maternal assessment for blood pressure, urine output, severe features (every 8 hours)
• Daily maternal laboratory tesng (every other day once stable)
management aer 48 hours if • Disconnue magnesium prophylaxis during expectant management
• Serial fetal growth assessments (every 2 weeks), UA Doppler studies for fetal growth restricon
• Serial amnioc fluid assessments
no contraindicaons • Oral an-hypertensives to achieve bp <160 mm Hg systolic and < 110 mm Hg diastolic (See Table 4)

• 34 weeks gestaon
• Worsening maternal condion (symptoms, laboratory tesng, severe hypertension)

Preeclampsia
• Non-reassuring fetal tesng (biophysical profile ≤ 4/10 at least 2 occasions 6 hours apart, recurrent late or variable decels)
• Persistent oligohydramnios
Indicaons to deliver • Fetal growth restricon (can be individualized)
• Pulmonary edema
• Eclampsia
• Labor or rupture of membranes
• Placental abrupon

Fig. 3. Expectant management of suspected preeclampsia with severe features (<34 weeks). UA, umbilical artery.

307
308 Pauli & Repke

evaluation. Severe hypertension should be treated per protocol (Tables 3 and 4) and
serial blood pressure, urine output, and serum laboratory assessment should occur.
Patients who should not be expectantly managed include those with eclampsia,
disseminated intravascular coagulation, intrauterine fetal demise, uncontrollable hy-
pertension, placental abruption, and pulmonary edema. These patients should be sta-
bilized and delivered. Fetal gestation age less than the institution-determined limit of
viability (usually 23–24 weeks) is also an indication for delivery.
Short-term expectant management (continuous maternal and fetal monitoring with
administration of antenatal steroids for 48 hours) may be appropriate for certain pa-
tients at less than 33 6/7 weeks. These patients include those with HELLP syndrome,
abnormal umbilical artery Doppler studies, fetal growth restriction or oligohydramnios,
and renal dysfunction. Worsening of maternal or fetal status during this period may
warrant delivery regardless of the completion of the steroid course.
Continued expectant management at less than 34 weeks involves daily maternal
assessment with laboratory testing, serial blood pressure monitoring, and vigilance
for evolution of worsening severe features. Daily fetal assessment is also recommen-
ded with daily testing and serial growth, fluid, and Doppler assessment. Some patients
may be managed with oral antihypertensives (see Table 4) to achieve blood pressure
less than 160/110 mm Hg. Magnesium seizure prophylaxis should be discontinued
during this period of expectant management.
For patients with preeclampsia with severe features being managed expectantly,
delivery should occur by 34 weeks. Earlier delivery should occur for worsening of
the maternal or fetal condition. Change in symptoms, laboratory testing, or ability to
control hypertension in the patient should prompt delivery. Nonreassuring fetal
testing, persistent oligohydramnios, and labor are fetal indications for delivery. Devel-
opment of eclampsia, placental abruption, or pulmonary edema must be addressed
immediately, the patient stabilized, and then the patient should be delivered. Manage-
ment of fetal growth restriction in the context of severe preeclampsia is likely to require
early delivery as well, but management may be individualized.

Intrapartum Management of Preeclampsia

Induction of labor for vaginal delivery is generally recommended for otherwise stable
patients with a vertex fetus and no other obstetric contraindications. The likelihood of

Table 3
Acute antihypertensive therapy for severe hypertension

Drug Dosage Adverse Effects

Labetalol 10–20 mg IV initially, then 20–80 mg IV Bronchoconstriction
every 10–30 min up to a total of 300 mg Do not use in asthma or heart failure
1–2 mg/min IV infusion
Hydralazine 5 mg IV or IM, then 5–10 mg IV every Hypotension
20–40 min, 0.5–10 mg/h IV infusion Headache
Fetal distress
Nifedipine 10–20 mg orally Reflex tachycardia
Repeat in 30 min if needed, then Headache
10–20 mg orally every 2–6 h

Abbreviations: IM, intramuscular; IV, intravenous.

Data from American College of Obstetricians and Gynecologists, Task Force on Hypertension in
Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gyne-
cologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013;122(5):1122–31.
 Preeclampsia 309

Table 4
Oral antihypertensive therapy

Labetalol 200 to 2400 mg/d

2 or 3 divided doses
Nifedipine 10 to 20 mg every 6 hours
30 to 120 mg daily (slow release)
Methyldopa 0.5 to 3 g/d
2 or 3 divided doses
Thiazide diuretics Dose depends on formulation
Second-line agent

Data from American College of Obstetricians and Gynecologists, Task Force on Hypertension in
Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gyne-
cologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013;122(5):1122–31.

cesarean increases with decreasing gestational age (93%–97% for <28 weeks, 53%–
65% for 28–32 weeks, and 31%–38% at 32–34 weeks’ gestation)25 and the patient’s
wishes as well as maternal and fetal condition must be taken into account.
Universal magnesium prophylaxis for all patients with preeclampsia with severe
features is recommended during labor and for 24 hours postpartum. Any patient with
eclampsia should receive an intravenous magnesium bolus of 4 to 6 g with 1 to 2 g/h
maintenance for at least 24 hours. For patients with preeclampsia without severe
features, universal magnesium prophylaxis is not recommended because of lack of
evidence that it significantly prevents eclamptic seizures or development of severe
preeclampsia. This evidence was based on small, poorly powered studies.26,27 How-
ever, patients without severe features may progress in disease during labor and in
the postpartum period, and should be carefully monitored with blood pressures, labo-
ratory assessments, and clinical symptoms for development of severe features, and
started on magnesium as indicated.

Postpartum Management
An area that has received increased attention recently is postpartum hypertension, the
most common cause of which is gestational hypertension/preeclampsia or chronic
hypertension.4 This condition may be caused by persistence of the antenatal hyper-
tensive disorder, or is also potentially a de novo postpartum condition, leading to
the conclusion that delivery is not necessarily the immediate cure that it has previously
been claimed to be. The potential complications of postpartum hypertension and pre-
eclampsia are serious and can be life threatening, and include eclamptic seizure,
stroke, congestive heart failure, renal failure, and permanent disability. The risk of
this may persist for 4 weeks postpartum. Therefore, emphasis has shifted to continue
close monitoring of patients with preeclampsia for a longer period of time, as well as
patient and provider education regarding the signs and symptoms of postpartum
hypertension/preeclampsia.
Current recommendations take into account that blood pressure that initially
decreases after delivery may increase 3 to 6 days postpartum in patients with pre-
eclampsia or other hypertensive disorders. The current hypertension guidelines
suggest blood pressure monitoring for 72 hours postpartum and then again 7 to
10 days postpartum as well. Patients should be evaluated for other causes of hyper-
tension (eg, thyroid disease, adrenal disease, cardiomyopathy, lupus, hemolytic
uremic syndrome) Patients with persistent postpartum hypertension beyond 24 hours
should have any medications that could be exacerbating blood pressure (eg,
310 Pauli & Repke

vasoconstrictive medications, nonsteroidal antiinflammatory drugs) discontinued. Pa-

tients who have signs or symptoms of preeclampsia or HELLP syndrome should be
treated with magnesium prophylaxis for 24 hours. In addition, antihypertensives
should be started for persistent blood pressures greater than or equal to 150 mm
Hg systolic or greater than or equal to 100 mm Hg diastolic.4,28 Examples of appro-
priate antihypertensive regimens are listed in Table 4.
Prevention of preeclampsia
Multiple studies have explored potential therapies for prevention of preeclampsia,
including various antioxidant vitamins, calcium, and aspirin, as well as bed rest and
activity restriction. No single therapy has proved to be overwhelmingly effective, but
currently low-dose aspirin, as an antiplatelet and antiinflammatory agent, is the favor-
ite. The proposed mechanism is the improvement in the disruption of the prostacyclin-
thromboxane balance, reducing thromboxane-mediated vasoconstriction, as well an
improvement in placental perfusion and reduction in ischemia-mediated endothelial
damage.29
Several small studies showed reduced risk of preeclampsia and fetal growth restric-
tion in high-risk patients (eg, prior preeclampsia, chronic hypertension, renal disease,
diabetes) with low-dose aspirin (50–150 mg daily) given during pregnancy.30,31 The
large, randomized studies that followed did not show a significant benefit (although
a trend was seen), but several meta-analyses pooling the available data do support
the use of daily low-dose aspirin for prevention of preeclampsia and fetal growth re-
striction in high-risk women before 16 weeks. Risk reduction is reported as 10% to
20%.10,29,32,33 The current recommendation from ACOG is to offer low-dose aspirin
(60–80 mg daily starting in the late first trimester) to women with a prior birth at less
than 34 weeks caused by preeclampsia or more than 1 prior pregnancy with pre-
eclampsia, the justification of which is the low rate of adverse events from low-dose
aspirin and low number needed to treat (depending on the study, as low as about
50) to prevent 1 case of preeclampsia.4

LONG-TERM RISKS

Cardiovascular disease is the number 1 cause of mortality in the United States.34

Women with a history of preeclampsia have an increased risk of cardiovascular dis-
ease later in life, particularly if they have a history of early-onset, severe, or recurrent
preeclampsia.35 Gestational age at onset seems to be more significant than severity of
disease, because patients in the early-onset group have the highest risk. Overall, pre-
eclampsia leads to a 4-fold increase in risk for chronic hypertension and 2-fold in-
crease in stroke (fatal and nonfatal), venous thromboembolism, and ischemic heart
disease, as well as an increased risk of death.35
Women with prior preeclampsia have also been shown to have a higher number of
white matter lesions years after the index pregnancy.36 The association of these white
matter lesions with posterior reversible encephalopathy syndrome or neurologic
symptoms during the pregnancy was less clear. This group of women was also noted
to have higher blood pressure years after the pregnancy compared with women with
normotensive pregnancies, supporting prior data linking hypertension and white mat-
ter lesions in older populations. Visual disturbances affecting quality of life have been
elucidated 10 years after pregnancy. An even longer-reaching risk is the finding that
children of women with preeclampsia have higher blood pressure and an increased
risk of stroke.34
Endothelial damage caused by preeclampsia may be the initial event that triggers
the development of atherosclerosis later in life. In addition, patients with preeclampsia
 Preeclampsia 311

have higher levels of triglycerides and low-density lipoprotein cholesterol than normal
pregnancies, as well as longer persistence of insulin resistance in the postpartum
period.34 These factors may also contribute to increased risk of cardiovascular dis-
ease and diabetes in later life. Other associations between future cardiovascular dis-
ease and preeclampsia include common genetic and pathologic influences such as
obesity, metabolic syndrome, and renal disease that are known risk factors for
preeclampsia.

RECURRENCE RISK

Recurrence rates of preeclampsia range widely, from 15% to 65%, likely because of
the heterogeneity of the patient populations studied.37–40 Women with severe pre-
eclampsia in the second trimester are at increased risk of repeat preeclampsia, recur-
rence in the second trimester, chronic hypertension, and morbidity and mortality.37
The recurrence risk in women with a history of early-onset preeclampsia has been
shown to be related to chronic hypertension but not severity of the symptoms of the
initial pregnancy.38 Bramham and colleagues39 identified risk factors for recurrent pre-
eclampsia as black or Asian race, systolic blood pressure of greater than 130 mm Hg,
current antihypertensive use, baseline proteinuria, and prior delivery at less than
34 weeks. Obese and overweight women are also at increased risk of recurrent pre-
eclampsia.40 Recurrence risk has also been shown to be inversely proportional to
the gestational age at delivery of the index pregnancy.40

SUMMARY

Preeclampsia has threatened gravid patients and challenged the medical community
since ancient times. Clinicians currently have a reasonable understanding of how to
stratify patients based on risk of the disease or its recurrence as well as clear-cut
guidelines for diagnosis. However, there are limited measures to offer in the way of
prevention, and the fundamental cure beyond delivery continues to be elusive. Man-
agement of preeclampsia remains a challenge, because continuation of pregnancy for
amelioration of prematurity of the fetus places the mother at ever increasing risk of
potentially permanent or life-threatening complications. However, it is certain that
constant vigilance is essential throughout antepartum, intrapartum, and postpartum
care for signs and symptoms of development of the disease. Once the diagnosis
has been made, it is the responsibility of the health care provider and the patient to
continuously reevaluate the clinical status of both the patient and the fetus so that
effective intervention can be made to bring about safe outcomes.

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