Preeclampsia: Clinical features and diagnosis

Preeclampsia: Clinical features and diagnosis

Authors
Phyllis August, MD, MPH
Baha M Sibai, MD
Section Editor
Charles J Lockwood, MD
Deputy Editor
Vanessa A Barss, MD
Disclosures
All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Mar 2013. | This topic last updated: Jan 11, 2013.

INTRODUCTION Preeclampsia is a multi-system disorder characterized by

hypertension and proteinuria in the last half of pregnancy. Although most affected
pregnancies deliver at term or near term with good maternal and fetal outcomes, these
pregnancies are at increased risk for maternal and/orfetal mortality or serious
morbidity [ 1,2 ].

DEFINITIONS OF PREGNANCY-RELATED HYPERTENSIVE DISORDERS There

are four major hypertensive disorders related to pregnancy [ 3,4 ]:

Preeclampsia Preeclampsia refers to the new onset of hypertension and

proteinuria ( table 1 ) after 20 weeks of gestation in a previously
normotensive woman. Clinically, preeclampsia can be classified as severe
when severe hypertension, severe proteinuria, or other signs/symptomsof
end-organ injury are present ( table 2 ) [ 4,5 ]. In the absence of any of
these findings, preeclampsia can be classified as mild. In this commonly
used system, there is no moderate classification.

Eclampsia refers to the development of grand mal seizures in a woman with

preeclampsia, in the absence of other neurologic conditions that could
account for the seizure. (See "Eclampsia" .)

HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets)

probably represents a severe form of preeclampsia, but this relationship
remains controversial; HELLP may be an independent disorder. As many as
15 to 20 percent of affected patients do not have concurrent hypertension or
proteinuria, leading some experts to believe that HELLP syndrome is a
separate disorder from preeclampsia. (See "HELLP syndrome".)

Chronic/preexisting hypertension Chronic/preexisting hypertension is

defined as systolic pressure 140 mmHg and/or diastolic pressure 90
mmHg that antedates pregnancy or is present before the 20th week of
pregnancy (on at least two occasions) or persists longer than 12 weeks
 postpartum. It can be primary (essential hypertension) or secondary to a
variety of medical disorders. (See "Overview of hypertension in adults" .)

Preeclampsia superimposed upon chronic/preexisting hypertension

Superimposed preeclampsia is defined by the new onset of proteinuria after
20 weeks of gestation in a woman with chronic/preexisting hypertension. For
women with chronic/preexisting hypertension who have proteinuria prior to or
in early pregnancy, superimposed preeclampsia is defined by worsening or
resistant hypertension (especially acutely) in the last half of pregnancy or
development of signs/symptoms of severe preeclampsia ( table 2 ).

Gestational hypertension During pregnancy, gestational hypertension

refers to hypertension without proteinuria or other signs/symptoms of
preeclampsia that develops after 20 weeks of gestation ( table 3 ). It should
resolve by 12 weeks postpartum. If hypertension persists beyond 12 weeks
postpartum, the diagnosis is revised to chronic/preexisting hypertension that
was masked by the physiologic decrease in blood pressure that occurs in
early pregnancy. If hypertension resolves postpartum, the diagnosis is
revised to transient hypertension of pregnancy. (See "Gestational
hypertension" .)

INCIDENCE Preeclampsia occurs in up to 7.5 percent of pregnancies worldwide

[ 6,7 ]. Variations in incidence reflect, at least in part, differences in the maternal age
distribution and proportion of primiparous women among populations [ 2 ].

BURDEN OF DISEASE Women with preeclampsia are at an increased risk for life-
threatening events, including placental abruption, acute renal failure, cerebral
hemorrhage, hepatic failure or rupture, pulmonary edema, disseminated intravascular
coagulation, and progression to eclampsia. Worldwide, 10 to 15 percent of direct
maternal deaths (ie, resulting from obstetric complications of pregnancy) are
associated withpreeclampsia/eclampsia [ 8 ]. In the United
States, preeclampsia/eclampsia is one of four leading causes of maternal death, along
with hemorrhage, cardiovascular conditions, and thromboembolism [ 9-11 ]. There is
approximately one maternal death due to preeclampsia-eclampsia per 100,000 live
births, with a case-fatality rate of 6.4 deaths per 10,000 cases [ 12,13 ]. In the
Netherlands between 1993 and 2005, preeclampsia was the most common cause of
maternal death, with 3.5 maternal deaths per 100,000 live births [ 14 ].
(See "Overview of maternal mortality" .)

Morbidity and mortality are also increased for the fetus/neonate because of the greater
risk of restricted fetal growth and preterm birth in affected pregnancies.

RISK FACTORS Risk factors for preeclampsia are listed in the table ( table 4 ). The
magnitude of risk depends upon the specific factor and is described below for selected
risk factors evaluated in a systematic review of controlled studies [ 15 ].

A past history of preeclampsia increases the risk of developing preeclampsia in

a subsequent pregnancy seven-fold compared to women without this history
(RR 7.19, 95% CI 5.85-8.83) [ 15 ].
 The severity of preeclampsia strongly impacts this risk. Women with severe
second trimester preeclampsia are at greatest risk of developing
preeclampsia in a subsequent pregnancy: rates of 25 to 65 percent have
been reported [ 16-19 ]. By comparison, women with mild preeclampsia in
their first pregnancy develop preeclampsia in 5 to 7 percent of second
pregnancies [ 20,21 ]. Women who had a normotensive first delivery develop
preeclampsia in less than 1 percent of second pregnancies.

First pregnancy (nulliparity) (RR 2.91, 95% CI 1.28-6.61) [ 15 ]. It is unclear

why the primigravid state is a significant predisposing factor. One theory is
that these women may have had limited recent exposure to paternal
antigens, which may play a role in the pathogenesis of the disease.

A family history of preeclampsia in a first degree relative (RR 2.90, 95% CI

1.70-4.93) [ 15 ], suggesting a heritable mechanism in some cases [22,23 ].
The father of the baby may contribute to the increased risk, as the paternal
contribution to fetal genes may have a role in defective placentation and
subsequent preeclampsia. (See "Pathogenesis of preeclampsia", section on
'Genetic factors' .)

Preexisting medical conditions:

Pregestational diabetes (RR 3.56, 95% CI 2.54-4.99) [ 15 ], an effect that is

probably related to a variety of factors, such as underlying renal or vascular
disease, high plasma insulin levels/insulin resistance, and abnormal lipid
metabolism [ 24 ]. (See "Pregnancy risks in women with type 1 and type 2
diabetes mellitus" and "Prepregnancy evaluation and management of women
with type 1 or type 2 diabetes mellitus" .)

Blood pressure 130/80 mm Hg at the first prenatal visit (RR 1.38-2.37) [ 15 ].

The risk of superimposed preeclampsia is highest in women with diastolic
blood pressure 110 mm Hg (RR 5.2) and 100 mm Hg (RR 3.2) before 20
weeks of gestation.

Antiphospholipid antibodies (RR 9.72, 95% CI 4.34-21.75) [ 15 ].

(See "Obstetrical manifestations of the antiphospholipid syndrome" .)

Body mass index 26.1 (RR 2.47, 95% CI 1.66-3.67) [ 15 ]. (See "The impact
of obesity on fertility and pregnancy", section on 'Pregnancy associated
hypertension' .)

Twin pregnancies (RR 2.93, 95% 2.04-4.21) [ 15 ]. The risk increases with
increasing number of fetuses in multiple gestations: triplet pregnancy triples
the risk of preeclampsia compared with twin pregnancy.

Advanced maternal age (maternal age 40 RR 1.96, 95% CI 1.34-2.87 for

multiparas and RR 1.68, 95% CI 1.23-2.29 for primiparas) [ 15 ]. Older
women tend to have additional risk factors, such as diabetes mellitus and
chronic hypertension. Whether adolescents are at higher risk of preeclampsia
is more controversial [ 25 ]; a systematic review did not find an association
[ 15 ]. (See "Effect of advanced age on fertility and pregnancy in women" .)
Of note, women who smoke cigarettes have a lower risk of preeclampsia than
nonsmokers. (See "Smoking and pregnancy", section on 'Preeclampsia' .)

OVERVIEW OF PATHOPHYSIOLOGY The pathophysiology of preeclampsia likely

involves both maternal and fetal/placental factors. Abnormalities in the development of
the placental vasculature early in pregnancy, weeks to months before development of
clinical manifestations of the disease, are well-documented [ 26,27 ]. These
abnormalities can result in placental underperfusion, and possibly hypoxia and
ischemia. Observational data support the hypothesis that placental underperfusion,
hypoxia, and/or ischemia may lead to release of circulating antiangiogenic factors
(soluble fmslike tyrosine kinase [sFlt-1], soluble endoglin [sEng]) and other
substances that can cause widespread maternal systemic endothelial dysfunction
(increased vascular permeability, vasoconstriction, activation of coagulation system,
microangiopathic hemolysis), resulting in hypertension, proteinuria, and the other
clinical manifestations of preeclampsia [ 28 ]. The severity of the disease is influenced
primarily by maternal and pregnancy-specific factors, but paternal and environmental
factors may also play a role [ 29 ]. (See "Pathogenesis of preeclampsia" .)

CLINICAL MANIFESTATIONS

Clinical presentation The new development of hypertension and proteinuria after

20 weeks of gestation is usually due to preeclampsia, particularly in a nulliparous
woman. In most women, these findings first become apparent after 34 weeks of
gestation, including when the woman is in labor (ie, late onset preeclampsia)
[ 30,31 ]. In about 10 percent of women, hypertension and proteinuria develop before
34 weeks of gestation (ie, early onset preeclampsia) [ 30 ], and in about 5 percent,
preeclampsia is first recognized postpartum (ie, postpartum preeclampsia), usually
within 48 hours of delivery [ 32-34 ].

The degree of maternal hypertension and proteinuria, and the presence/absence of

other clinical manifestations of the disease are highly variable [ 35 ]. Most patients
have only mild hypertension (140/90 and <160/110 mm Hg) and mild proteinuria
(<5 grams in 24 hours), usually accompanied by peripheral edema. About 25 percent
develop one or more of the following nonspecific findings:

Signs and symptoms

Severe hypertension (systolic blood pressure 160 mm Hg or diastolic 110

mm Hg on two occasions at least six hours apart)

Persistent and/or severe headache,

Visual abnormalities (scotomata, photophobia, blurred vision, or temporary

blindness [rare])

Upper abdominal or epigastric pain

Nausea, vomiting
 Oliguria

Dyspnea, retrosternal chest pain

Fetal growth restriction

Oligohydramnios

Altered mental status

Laboratory abnormalities

Hemoconcentration

Microangiopathic hemolytic anemia (abnormal peripheral smear, elevated

bilirubin, or low serum haptoglobin levels U/L)

Thrombocytopenia (<100,000/microL)

Elevated serum creatinine concentration (>1.3 mg/dL)

Elevated liver enzymes (twice the upper limit of normal)

Severe proteinuria (5 grams in 24 hours)

Atypical presentation Atypical presentations include any of the following

[ 34,36 ]:

Onset of signs/symptoms at <20 weeks of gestation

Hypertension or proteinuria (but not both) with or without characteristic signs

and symptoms of severe preeclampsia

Delayed postpartum onset or exacerbation of disease (>2 days postpartum)

Onset <20 weeks Preeclampsia prior to 20 weeks of gestation is usually

associated with a complete or partial molar pregnancy. (See"Gestational trophoblastic
disease: Epidemiology, clinical manifestations and diagnosis" .) Rarely, characteristic
signs and symptoms before 20 weeks have been attributed to severe preeclampsia
after other disorders with similar findings (eg, lupus nephritis, thrombotic
thrombocytopenic purpura, hemolytic-uremic syndrome, antiphospholipid syndrome,
acute fatty liver of pregnancy) were excluded. (See 'Differential diagnosis' below.)

Hypertension or proteinuria (not both) Hypertension or proteinuria (but not

both) with characteristic signs and symptoms of severe preeclampsia is uncommon,
but may be observed in 15 percent of patients with HELLP syndrome and in some
patients with eclampsia. (See "Eclampsia", section on 'Can eclampsia be
predicted?' and "HELLP syndrome" .)
Women with hypertension or proteinuria (but not both) may go on to develop
preeclampsia. No prospective studies have been performed in pregnant women with
isolated gestational proteinuria to determine their risk of developing preeclampsia later
in pregnancy. Between 15 and 25 percent of women with gestational hypertension
subsequently develop preeclampsia. (See "Gestational hypertension", section on 'Risk
of progression to preeclampsia' .)

Delayed postpartum onset or exacerbation of disease Delayed postpartum

preeclampsia can be defined as signs and symptoms of the disease leading to
readmission more than two days but less than six weeks after delivery [ 34 ], although
various other definitions have been used. In a retrospective cohort study including 152
patients with delayed postpartum preeclampsia, 63.2 percent had no antecedent
diagnosis of hypertensive disease in the current pregnancy, whereas 18.4 percent had
preeclampsia, 9.2 percent had chronic hypertension, 4.6 percent had gestational
hypertension, and 4.6 percent had preeclampsia superimposed on chronic hypertension
during the peripartum period [ 34 ]. Of these patients, 14.5 percent developed
postpartum eclampsia.

Course Most women have only mild hypertension and mild proteinuria that
gradually worsen until delivery. In about 25 percent of women, especially those with
early onset preeclampsia, hypertension and/or proteinuria reach a severe
level and/or signs and symptoms of end-organ damage become apparent over a period
of days to weeks ( table 2 ) [ 37 ]. Two percent of these women develop eclampsia.

Severe preeclampsia can be associated with serious maternal and/or fetal sequelae
(eg, abruptio placentae; liver hematoma or rupture; disseminated intravascular
coagulation; stroke; need for mechanical ventilation, invasive hemodynamic
monitoring, transfusion, or dialysis) [ 38,39 ]. It is important to note that severe
sequelae can occur in women with mild hypertension and mild proteinuria who have
clinical evidence of significant end-organ dysfunction. Chest pain, dyspnea, low oxygen
saturation, low platelet count, and elevated creatinine and aspartate transaminase
concentrations appear to be particularly predictive of adverse outcome [ 40 ].

Delivery of the placenta always results in complete resolution of signs and symptoms
of the disease. Typically, mobilization of third-space fluid and diuresis begin within 48
hours of delivery. Hypertension may worsen during the first, and occasionally the
second, postpartum week, but normalizes in most women within four weeks
postpartum [ 41 ]. Rarely, hypertension persists beyond three months. Proteinuria
usually begins to improve within a few days, however, in women with several grams of
protein excretion, complete resolution may take weeks to months; a prolonged time to
complete resolution is more likely with severe disease [ 42 ]. Delayed postpartum
onset or exacerbation of disease is atypical (see 'Delayed postpartum onset or
exacerbation of disease' above).

Clinical features and pathophysiology by organ system

Cardiopulmonary
Hypertension Hypertension is generally the earliest clinical finding of preeclampsia
and is the most common clinical clue to the presence of the disease. The blood
pressure usually rises gradually, reaching the hypertensive range (140/90 mmHg)
sometime in the third trimester, often after the 37th week of gestation [ 30 ]. However,
in some women, hypertension develops rapidly or before 34 weeks of gestation or
postpartum. A systolic blood pressure of 160 mm Hg or diastolic blood pressure of
110 mm Hg on two occasions at least six hours apart upstages preeclampsia from
mild to severe [ 4 ].

Intravascular volume and edema Intravascular volume is reduced in

preeclampsia. There is no evidence of underfilling of the arterial circulation; rather, the
reduced volume appears to be a consequence of vasoconstriction from enhanced
responses to vasoactive substances. This issue has not been conclusively resolved.

Edema in preeclampsia may be due to capillary leaking or represent "overfill" edema.

Many pregnant women have edema, whether or not they have preeclampsia. However,
sudden and rapid weight gain (eg, >5 pounds/week) and facial edema are more
common in women who develop preeclampsia, thus, these findings warrant evaluation
for other clinical manifestations of disease.

Cardiac function Preeclampsia does not affect the myocardium directly, but the
heart responds to physiological changes induced by preeclampsia. Left ventricular
ejection fraction usually remains within normal limits [ 43 ], but reductions in
longitudinal, circumferential, and radial systolic strain have been observed [ 44 ]. The
decrement in left ventricular performance in women with preeclampsia has been
attributed to a physiologic response to increased afterload [ 43-45 ], but other factors
may play a role since systolic strain was depressed in preeclamptic patients compared
to pregnant women with nonproteinuric hypertension with similar resting blood
pressure [ 44 ]. The high afterload in preeclampsia is associated with elevated cardiac
filling pressures, reflected by four-fold higher concentrations of natriuretic peptides in
women with preeclampsia compared to pregnant women who are normotensive or
have chronic hypertension [ 46 ].

Severe preeclampsia can be associated with a highly variable hemodynamic profile

[ 45-49 ]. A small subgroup of women with severe preeclampsia develops myocardial
damage or global diastolic dysfunction [ 50 ]. Troponin I levels should be obtained
when clinically indicated, such as when the patient complains of chest pain suggestive
of myocardial ischemia or new electrocardiogram changes are observed [ 51,52 ].
Preeclampsia is not associated with elevated troponin levels in the absence of cardiac
disease [ 53 ].

Pulmonary edema The presence of pulmonary edema upstages the diagnosis

from mild to severe preeclampsia. The etiology of pulmonary edema in preeclampsia is
multifactorial [ 54-57 ]. Excessive elevation in pulmonary vascular hydrostatic pressure
compared with plasma oncotic pressure may produce pulmonary edema in some
women, particularly in the postpartum period. However, not all preeclamptic patients
with pulmonary edema demonstrate this phenomenon. Other causes of pulmonary
edema are capillary leak, left heart failure, and iatrogenic volume overload.
Renal The kidney is the organ most likely to manifest endothelial injury related to
preeclampsia.

Proteinuria Proteinuria in preeclampsia is defined as 0.3 grams protein in a 24-

hour urine specimen or persistent 1+ (30 mg/dL) on dipstick or a random
protein:creatinine ratio >30 mg/mmol. The presence of 5 grams of protein in a 24-
hour urine collection upstages preeclampsia from mild to severe. Although proteinuria
in women with preeclampsia is most often in the mild to moderate range (<5 g),
preeclampsia remains the most common cause of severe proteinuria in pregnant
women; levels of proteinuria >10 g/day may be seen. (See "Evaluation of proteinuria
in pregnancy" .)

Urinary protein excretion may be a late finding [ 58,59 ], but generally increases as
preeclampsia progresses. It is due, in part, to impaired integrity of the glomerular
barrier and altered tubular handling of filtered proteins (hypofiltration) leading to
increased protein excretion [ 60 ]. Both size and charge selectivity of the glomerular
barrier are affected [ 61 ]. Using special studies, podocyturia (urinary excretion of
podocytes) has been observed in patients with preeclampsia [ 62 ]. Urinary shedding
of podocytes may indicate podocyte loss from the glomerulus, which may lead to a
disruption of the glomerular filtration barrier and consequent proteinuria. Deficient
vascular endothelial growth factor (VEGF) signaling appears to account, at least in
part, for these effects. (See "Pathogenesis of preeclampsia", section on 'Pathogenesis
of systemic endothelial dysfunction' .)

Renal function Glomerular filtration rate (GFR) decreases by 30 to 40 percent in

preeclampsia compared to pregnant normotensive controls; renal plasma flow also
decreases, but to a lesser degree. The plasma creatinine concentration is generally
normal or only slightly elevated (1.0 to 1.5mg/dL [88 to 133 micromol/L]). A rising
creatinine and oliguria, ie, urine output <500 mL/24 hours, indicates severe disease
and results from renal vasoconstriction and sodium retention due to reduced plasma
volume and systemic vasoconstriction. (See "Acute kidney injury (acute renal failure)
in pregnancy", section on 'Preeclampsia' .)

Hyperuricemia and hypocalciuria are also observed; the mechanisms for these changes
are not clear [ 60,63,64 ]. The rise in serum uric acid concentration is thought to
reflect increased proximal sodium resorption and, secondarily, urate reabsorption
induced by renal ischemia. Other possible mechanisms for hyperuricemia in
preeclampsia include underlying metabolic syndrome, tissue damage, oxidative stress,
and inflammation [ 65 ].

Although hyperuricemia is associated with preeclampsia, serum uric acid level is a poor
predictor of development of the disease or maternal and fetal complications in women
with preeclampsia [ 66,67 ]. However, an elevated uric acid level (>6.0 mg/dL) at the
time of diagnosis appears to identify women at risk of delivery within seven days,
whereas a low uric acid level (4.0 mg/dL) is associated with a prolonged latency
period [ 68 ].

Urine sediment The urine sediment is typically benign.

Renal histology The renal histologic changes described in women with
preeclampsia who have had kidney biopsies, and in autopsy specimens obtained from
women who died of eclampsia, are termed glomerular endotheliosis. Light and
electron microscopy of glomerular endotheliosis show the following ( picture 1A-C )
[ 69 ]:

Endothelial cell swelling

Loss of fenestrations

Occlusion of capillary lumens

Foot process effacement is not a prominent feature, despite marked proteinuria.

Glomerular endotheliosis shares histologic features with non-preeclamptic thrombotic

microangiopathies [ 69 ], except thrombi are rare in preeclampsia (although fibrin
deposition may be observed by immunofluorescence microscopy). Rarely, it may be
present without proteinuria and in nonpregnant women [ 70,71 ].

Hematologic The most common coagulation abnormality in preeclampsia is

thrombocytopenia. Microangiopathic endothelial injury and activation result in
formation of platelet and fibrin thrombi in the microvasculature. Accelerated platelet
consumption leads to thrombocytopenia; immune mechanisms may also play a role
[ 72 ]. A platelet count less than 100,000/microL upstages preeclampsia from mild to
severe.

The prothrombin time, partial thromboplastin time, and fibrinogen concentration are
not affected unless there are additional complications, such as abruptio placentae or
severe liver dysfunction [ 73 ].

Microangiopathic hemolysis may also occur and is detected by examination of a blood

smear for schistocytes and helmet cells ( picture 2A-B ) or elevation in the serum
lactate dehydrogenase concentration. Hemoconcentration may result from reduction of
plasma volume from capillary leaking. Hemolysis is associated with a low hematocrit,
while hemoconcentration is associated with a high hematocrit; when both hemolysis
and reduced plasma volume are present, the effects on hematocrit may negate each
other, resulting in a normal value. (See "Thrombocytopenia in
pregnancy" and "Abnormalities of coagulation and platelet function in preeclampsia" .)

The white blood cell count may be slightly higher due to neutrophilia [ 74 ].

Hepatic Periportal and sinusoidal fibrin deposition and microvesicular fat deposition
are histologic findings observed in the livers of preeclamptic women [ 75,76 ]. Reduced
hepatic blood flow can lead to ischemia and periportal hemorrhage. The clinical
manifestations of hepatic dysfunction include right upper quadrant or epigastric pain,
elevated transaminase levels, coagulopathy, and, in the most severe cases,
subcapsular hemorrhage or hepatic rupture. These hepatic changes upstage the
preeclampsia from mild to severe. Nausea and vomiting may occur.
Epigastric pain is one of the cardinal symptoms of severe preeclampsia. A review of
this nonspecific symptom revealed that it is typically experienced as a severe constant
pain that begins at night, usually maximal in the low retrosternum or epigastrium, but
may radiate to the right hypochondrium or back [77 ]. The pain is thought to be due to
stretching of Glissons capsule due to hepatic swelling or bleeding. It may be the only
symptom on presentation, thus a high index of suspicion is important to make the
diagnosis of preeclampsia rather than gastroesophageal reflux, which is common in
pregnant women, especially at night. The liver may be tender to palpation.

Rarely, transient diabetes insipidus has been reported in preeclampsia with hepatic
dysfunction. (See "Renal and urinary tract physiology in normal pregnancy", section on
'DI associated with hepatic dysfunction' .)

Acute pancreatitis is an even rarer complication of severe preeclampsia [ 78 ].

Central nervous system and eye Central nervous system manifestations of

preeclampsia include headache, visual symptoms, and generalized hyperreflexia;
sustained ankle clonus may be present.

Headache in preeclampsia may be temporal, frontal, occipital, or diffuse [ 79,80 ]. It is

usually a throbbing/pounding pain, but may be piercing pain. Although not
pathognomonic, a feature that suggests preeclampsia-related headache rather than
another type of headache is that it persists despite administration of over-the-counter
analgesics and it may become severe (ie, incapacitating, "the worst headache of my
life").

Visual symptoms are caused, at least in part, by constriction of retinal arteries.

Symptoms include blurred vision, flashing lights (photopsia), and scotomata (dark
areas or gaps in the visual field) [ 81-83 ]. Diplopia or amaurosis fugax (blindness in
one eye) may also occur. Cortical blindness is rare and typically transient [ 84 ].
Blindness related to retinal pathology, such as retinal artery or venous thrombosis,
retinal detachment, optic nerve damage, retinal artery spasm, and retinal ischemia,
may be permanent [ 85 ].

Seizures in a preeclamptic woman signify a change in diagnosis to eclampsia. One in

400 mildly preeclamptic and 1 in 50 severely preeclamptic women develop eclamptic
seizures.

Histopathologic correlates include hemorrhage, petechiae, cerebral edema,

vasculopathy, ischemic brain damage, microinfarcts, and fibrinoid necrosis [86,87 ].

The cerebrovascular manifestations of severe preeclampsia are poorly understood.

Cerebral edema and ischemic/hemorrhagic changes in the posterior hemispheres
observed on computed tomography and magnetic resonance imaging help to explain,
but do not fully account for, the clinical findings [88,89 ]. These findings may result
from vasospasm of the cerebral vasculature in response to severe hypertension or may
result from loss of cerebrovascular autoregulation leading to areas of both
vasoconstriction and forced vasodilation and thus represent a form of posterior
reversible leukoencephalopathy syndrome (PRES) [ 90,91 ]. PRES is typically
associated with severe hypertension, but can occur with rapid increases in blood
pressure in patients with endothelial damage [ 92 ]. (See "Reversible posterior
leukoencephalopathy syndrome" and "Eclampsia", section on 'Clinical manifestations
and diagnosis' .)

Stroke leading to death or disability is the most serious complication of

severe preeclampsia/eclampsia, but is rare.

Fetus and placenta The fetal consequences of chronic placental hypoperfusion are
fetal growth restriction and oligohydramnios. Fetal growth restriction upstages
preeclampsia from mild to severe.

Severe and early onset preeclampsia result in the greatest decrements in birth weight
compared to normotensive pregnancies, 12 and 23 percent, respectively [ 93 ]. By
comparison, late onset preeclampsia can be associated with higher than average birth
weight, possibly related to greater placental perfusion due to elevated cardiac output
sometimes observed with late onset disease [ 94-98 ]. However, this association may
also be the result of confounders associated with both preeclampsia and birth of large
for gestational age infants (eg, obesity, impaired glucose tolerance) [ 99 ].

Indicated preterm delivery is a secondary result of fetal or maternal complications.

Preeclampsia does not appear to accelerate fetal maturation, as once believed. The
frequency of neonatal morbidities such as respiratory distress, intraventricular
hemorrhage, and necrotizing enterocolitis is similar in infants of preeclamptic women
and age-matched nonhypertensive controls [ 100 ].

Abruptio placenta is infrequent (less than 1 percent) in women with mild preeclampsia,
but has been reported in 3 percent of those with severe disease [101 ]. (See "Placental
abruption: Clinical features and diagnosis" .)

Impaired placentation can lead to increased impedance to flow in the uterine arteries,
manifested by elevation of the pulsatility index accompanied by uterine artery notching
on uterine artery Doppler velocimetry. However, this finding is neither sensitive nor
specific for preeclampsia. (See "Prediction of preeclampsia", section on 'Uterine artery
Doppler velocimetry' .)

Increased resistance in the placental vasculature is also reflected by rising Doppler

indices of the umbilical artery. Absent and reversed end diastolic flow are the most
severe abnormalities and associated with a poor perinatal outcome. (See "Doppler
ultrasound of the umbilical artery for fetal surveillance" .)

Placental histology is described separately. (See "Histopathology of placental

disorders", section on 'Placental "underperfusion"' .)

Fetal hydrops (nonimmune or immune) can result in maternal symptoms identical to

those seen in typical preeclampsia. This disorder is called mirror or Ballantyne
syndrome and resolves without delivery if hydrops resolves. (See "Nonimmune hydrops
fetalis", section on 'Mirror syndrome' .)
DIAGNOSIS International guidelines generally agree that the diagnosis of
preeclampsia should be made in a previously normotensive woman with new onset of
hypertension and proteinuria after 20 weeks of gestation [ 4,5,74,102,103 ]. Criteria
for diagnosis are:

Systolic blood pressure 140 mmHg or diastolic blood pressure 90

mmHg, and

Proteinuria 0.3 grams in a 24-hour urine specimen or protein:creatinine ratio

0.3 mg/mg or >30 mg/mmol

Initial assessment for proteinuria is commonly performed by dipping a paper test strip
into a fresh clean voided midstream urine specimen. Proteinuria +1 on dipstick
should be confirmed by quantitative assessment (24 urine collection or
protein:creatinine ratio). (See "Evaluation of proteinuria in pregnancy" .)

Mildly elevated blood pressure should be documented by at least two measurements at

least four hours apart; asymptomatic outpatients with mild hypertension can be
reassessed within three to seven days [ 4 ]. The technique for blood pressure
measurement is described separately. (See "Blood pressure measurement in the
diagnosis and management of hypertension in adults" .)

For women with chronic/preexisting hypertension who have proteinuria prior to or in

early pregnancy, superimposed preeclampsia is difficult to diagnose definitively, but
should be suspected when there is a significant worsening of hypertension (especially
acutely) in the last half of pregnancy or development of signs/symptoms associated
with severe preeclampsia ( table 2 ).

Post-diagnostic evaluation The purpose of the post-diagnostic evaluation is to

determine the severity of disease and assess maternal and fetal well-being. These
factors, as well as gestational age, guide management. (See "Preeclampsia:
Management and prognosis" .)

Preeclampsia is generally classified as severe if any of the following are present in a

woman with preeclampsia [ 3-5,74,102-104 ]:

Severe hypertension (systolic blood pressure 160 mm Hg or diastolic blood

pressure 110 mm Hg on two occasions at least six hours apart)

Severe proteinuria (5 grams/day)

Signs/symptoms of end-organ injury ( table 2 )

Therefore, the history and physical examination should evaluate the patient for:

Persistent and/or severe headache

Visual abnormalities (scotomata, photophobia, blurred vision, or temporary

blindness)
 Upper abdominal or epigastric pain

Nausea, vomiting

Oliguria

Dyspnea

Altered mental status

The minimum post-diagnostic laboratory/imaging evaluation should include:

Platelet count

Serum creatinine

Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT)

Obstetrical ultrasound (fetal weight, amniotic fluid volume)

Fetal assessment (biophysical profile or nonstress test)

Additional tests that can be informative include blood smear and serum lactate
dehydrogenase (LDH) and bilirubin concentrations. Microangiopathic hemolysis is
suggested by elevated LDH and indirect bilirubin levels and red cell fragmentation
(schistocytes or helmet cells) on peripheral blood smear (picture 2A-B ).
Hemoconcentration occurs in preeclampsia, but hemolysis, if present, can decrease the
hematocrit to normal or anemic levels.

Coagulation function tests (eg, prothrombin time, activated partial thromboplastin

time, fibrinogen concentration) are usually normal if there is no thrombocytopenia or
liver dysfunction; therefore, they are not checked routinely [ 105 ].

Differential diagnosis

Preexisting hypertension versus mild preeclampsia Because of the reduction

in blood pressure that typically occurs early in pregnancy, a woman with preexistent
hypertension may be normotensive when first seen by the obstetrical provider. Later in
pregnancy when her blood pressure returns to its prepregnancy baseline, she may
appear to be developing mild preeclampsia if there are no documented prepregnancy
blood pressure measurements.

In this setting, a variety of factors can be helpful in establishing the likely diagnosis:

Hypertension occurring before the 20th week is usually due to preexisting

hypertension rather than to preeclampsia.

Proteinuria is present and increases with time in preeclampsia, occasionally

reaching the nephrotic range; by comparison, protein excretion is usually
 absent or less than 1 g/day in hypertensive nephrosclerosis [ 20 ].
(See "Clinical features, diagnosis, and treatment of hypertensive
nephrosclerosis" .)

Preeclampsia is more common in nulliparas than in multiparas.

Preeclampsia is more common in older (>40 years) nulliparas, although these

women are also more likely to have preexisting hypertension, as are older
multiparous women (see 'Risk factors' above).

Normally, plasma uric acid concentration decreases in early pregnancy and then
increases [ 106,107 ]. Preeclampsia is typically associated with a rise in the plasma
urate level to above 5.5 to 6 mg/dL (327 micromol/L) [ 108 ]. The plasma urate
concentration tends to remain below this level in preexisting hypertension, unless the
patient is taking diuretics or has superimposed preeclampsia [ 107 ].

Superimposed preeclampsia In women with known primary (essential)

hypertension and increasing blood pressure and/or proteinuria, the presence of
systemic manifestations of severe preeclampsia, such as thrombocytopenia, hemolysis,
increased serum levels of aminotransferases, and visual symptoms strongly suggest
development of superimposed preeclampsia ( table 2 ) [ 109 ]. In the absence of
features of severe preeclampsia, an elevated uric acid level (5.5 mg/dL) supports the
diagnosis of superimposed preeclampsia [ 107,110 ]. Reproductive age women with
primary (essential) hypertension typically have no or mild proteinuria so severe
proteinuria suggests development of superimposed preeclampsia.

Exacerbation of preexisting renal disease Superimposed preeclampsia

frequently develops in women with preexisting primary or secondary renal disease
[ 111,112 ]. However, worsening hypertension and proteinuria in a woman with
preexisting renal disease may also represent an exacerbation of the underlying disease
or the physiological effects of pregnancy. The ability to accurately distinguish among
these possibilities is important, as management and complications are different.

Significant clues to the diagnosis of severe preeclampsia are the presence of systemic
manifestations of the disorder, such as thrombocytopenia, increased serum levels of
aminotransferases, and visual symptoms ( table 2 ) [ 109 ]. Onset of disease in the
first half of pregnancy suggests exacerbation of underlying renal disease, rather than
preeclampsia.

Laboratory evidence suggestive of exacerbation of renal disease includes the presence

of findings specific for disease activity (eg, low complement levels in a patient with
systemic lupus erythematosus, urinalysis consistent with a proliferative glomerular
disorder [red and white cells and/or cellular casts]). An active urine sediment is not a
feature of preeclampsia. (See "Pregnancy in women with underlying renal
disease" and "Pregnancy in women with diabetic nephropathy" .)

Antiphospholipid syndrome Hypertension, proteinuria, and thrombocytopenia,

and other signs of end-organ dysfunction can be seen in antiphospholipid syndrome.
The absence of laboratory evidence of antiphospholipid antibodies excludes this
diagnosis. (See "Clinical manifestations of the antiphospholipid
syndrome" and "Diagnosis of the antiphospholipid syndrome" and "Obstetrical
manifestations of the antiphospholipid syndrome" .)

AFLP, TTP, HUS, SLE Although preeclampsia/HELLP is the most common cause of
hypertension, thrombocytopenia, liver abnormalities, and renal abnormalities in
pregnant women, the following conditions should be considered and excluded, if
possible. Laboratory findings in these disorders are compared in the tables ( table 5A-
B ).

Acute fatty liver of pregnancy (AFLP). Low grade fever can be present in AFLP,
but does not occur in preeclampsia/HELLP. AFLP is associated with more
serious liver dysfunction: hypoglycemia and disseminated intravascular
coagulation are common features, while unusual inpreeclampsia/HELLP. AFLP
is also usually associated with more significant renal dysfunction compared
to preeclampsia/HELLP. (See "Acute fatty liver of pregnancy" .)

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS).

Although neurologic abnormalities and acute renal failure are more prominent
in TTP-HUS, this disorder may be indistinguishable from
severe preeclampsia/HELLP syndrome. Fever and
thrombocytopenia<20,000/microL support a diagnosis of
TTP. Preeclampsia/HELLP begins to resolve within 48 hours after delivery,
while HUS has a more protracted postpartum course, and patients develop
severe renal failure in the postpartum period. (See "Diagnosis of thrombotic
thrombocytopenic purpura-hemolytic uremic syndrome in adults" .)

Exacerbation of systemic lupus erythematosus (SLE). Flares of SLE are likely to

be associated with hypocomplementemia and increased titers of anti-DNA
antibodies; by comparison, complement levels are usually, but not always,
normal or increased in preeclampsia. (See "Pregnancy in women with
systemic lupus erythematosus" .)

In the future, measurement of urinary or plasma angiogenic factors (soluble fms-like

tyrosine kinase, placental growth factor) may be useful in distinguishing preeclampsia
from other hypertensive-proteinuric disorders, but this test is investigational and not
readily available [ 113-115 ]. (See"Pathogenesis of preeclampsia", section on 'sFlt-1,
VEGF, PIGF' .)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education

materials, The Basics and Beyond the Basics. The Basics patient education pieces
are written in plain language, at the 5 th to 6 th grade reading level, and they answer the
four or five key questions a patient might have about a given condition. These articles
are best for patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more sophisticated,
and more detailed. These articles are written at the 10 th to 12 th grade reading level
and are best for patients who want in-depth information and are comfortable with
some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage
you to print or e-mail these topics to your patients. (You can also locate patient
education articles on a variety of subjects by searching on patient info and the
keyword(s) of interest.)

Basics topics (see "Patient information: Preeclampsia (The Basics)" and "Patient
information: High blood pressure and pregnancy (The Basics)" and"Patient
information: HELLP syndrome (The Basics)" )

Beyond the Basics topics (see "Patient information: Preeclampsia (Beyond the
Basics)" )

SUMMARY AND RECOMMENDATIONS

The four major hypertensive disorders related to pregnancy are preeclampsia,

chronic hypertension, preeclampsia superimposed upon chronic hypertension,
and gestational hypertension ( table 3 ). (See 'Definitions of pregnancy-
related hypertensive disorders' above.)

Major risk factors for development of preeclampsia include past history of

preeclampsia, nulliparity, pregestational diabetes, chronic hypertension,
obesity, family history of preeclampsia, and multiple gestation. (See 'Risk
factors' above.)

The gradual development of hypertension and proteinuria in the last half of

pregnancy is usually due to preeclampsia, particularly in a nullipara. These
findings typically become apparent after 34 weeks of gestation and progress
until delivery, but some women develop symptoms earlier in gestation,
intrapartum, or postpartum. (See 'Clinical presentation' above.)

The diagnosis of preeclampsia is based on the new onset of hypertension and

proteinuria after 20 weeks of gestation in a previously normotensive woman
(see 'Diagnosis' above):

Systolic blood pressure 140 mmHg or diastolic blood pressure 90

mmHg, and

Proteinuria 0.3 grams in a 24-hour urine specimen or protein:creatinine ratio

>30 mg/mmol

The goal of the post-diagnostic evaluation is to determine the severity of

disease and assess maternal and fetal well-being. Criteria for severe disease
are listed in the table ( table 2 ). Post-
diagnostic laboratory/imaging evaluation should include (see 'Post-diagnostic
evaluation' above):

Platelet count

Serum creatinine
 Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT)

Obstetrical ultrasound (fetal weight, amniotic fluid volume)

Fetal assessment (biophysical profile or nonstress test)

Differential diagnosis includes exacerbation of underlying renal disease, acute

fatty liver of pregnancy, thrombotic thrombocytopenic purpura-hemolytic
uremic syndrome, and exacerbation of systemic lupus erythematosus.
(See 'Differential diagnosis' above.)

REFERENCES

Preeclampsia: Management and prognosis

Preeclampsia: Management and prognosis

Authors
Errol R Norwitz, MD, PhD
John T Repke, MD
Section Editor
Charles J Lockwood, MD
Deputy Editor
Vanessa A Barss, MD
Disclosures
All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Mar 2013. | This topic last updated: Mar 25, 2013.

INTRODUCTION Preeclampsia refers to the new onset of hypertension and

proteinuria after 20 weeks of gestation in a previously normotensive woman ( table
1 ). It can be classified as mild or severe ( table 2 ). Delivery results in resolution of
the disease.

OVERVIEW OF MANAGEMENT The definitive treatment of preeclampsia is

delivery to prevent development of maternal or fetal complications from disease
progression. (See "Preeclampsia: Clinical features and diagnosis", section on 'Burden
of disease' .) Whether or not to deliver the fetus is based upon gestational age, the
severity of preeclampsia, and maternal and fetal condition. Patients with mild or severe
preeclampsia at or near term are delivered; however, remote from term, the risks of
serious sequelae from disease progression need to be weighed against the risks of
preterm birth. Evidence of serious maternal end-organ dysfunction or nonreassuring
tests of fetal well-being are indications for prompt delivery at any gestational age. On
the other hand, when mother and fetus are stable, a conservative approach is
reasonable in order to achieve further fetal growth and maturity.

APPROACH BASED ON DISEASE SEVERITY

Severe preeclampsia Severe preeclampsia ( table 2 ) is generally regarded as an

indication for delivery, regardless of gestational age, in order to minimize the risk of
development of serious maternal and fetal complications (eg, cerebral hemorrhage,
hepatic rupture, renal failure, pulmonary edema, seizure, bleeding related to
thrombocytopenia, fetal growth restriction, abruptio placentae) [ 1-4 ]. With the
exception of fetal growth restriction, any of these adverse events can occur suddenly in
a woman with severe disease. However, if proteinuria 5 grams is the only criteria for
severe disease, patients are usually managed as mild preeclamptics since the amount
of proteinuria has no correlation with risk of adverse maternal or perinatal outcome
[ 5-8 ]. (See "Expectant management of severe preeclampsia", section on 'Severe
preeclampsia based solely on proteinuria' .) Similarly, if the only criteria for severe
disease is (1) mild fetal growth restriction with reassuring Doppler velocimetry or (2)
severe hypertension, then a conservative approach may be considered remote from
term. These clinical scenarios are discussed in detail separately. (See "Expectant
management of severe preeclampsia", section on 'Severe preeclampsia based solely on
fetal growth restriction' and "Expectant management of severe preeclampsia", section
on 'Severe preeclampsia based solely on blood pressure criteria' .)

Observational data suggest that the decision to expedite delivery in the setting of
severe preeclampsia does not mandate immediate cesarean birth [ 9,10]. Cervical
ripening agents can be used prior to induction if the cervix is not favorable [ 11 ].
However, we feel that a prolonged induction and inductions with a low likelihood of
success are best avoided. Cesarean delivery is reasonable for women with severe
preeclampsia who are under 30 weeks of gestation and have a low Bishop score, given
the high frequency of nonreassuring fetal heart rate tracings and failure of the cervix to
dilate in this setting [ 11-13 ]. Only about one-third of preterm inductions result in
vaginal birth.

Prolongation of pregnancy in a tertiary care setting or in consultation with a maternal-

fetal medicine specialist is an option for selected women remote from term (<34 weeks
of gestation). Candidates for this approach and their management (eg, antenatal
corticosteroids for fetal lung maturation) are discussed separately. (See "Expectant
management of severe preeclampsia" .)

Mild preeclampsia Experts consistently recommend delivery of women with mild

preeclampsia at 37 weeks of gestation [ 4,14,15 ]. Cervical ripening agents should be
used in women with unfavorable cervices.

The benefits of labor induction at 37 weeks of gestation were illustrated in a

multicenter trial (HYPITAT) that randomly assigned 756 women with mild
preeclampsia or gestational hypertension >36 0/7 weeks to induction of labor
or expectant management with maternal/fetal monitoring [ 16 ]. Routine
induction was associated with a significant reduction in composite adverse
maternal outcome (RR 0.71, 95% CI 0.59-0.86; absolute risk reduction
 12.76 percent), which was primarily driven by a reduction in patients who
developed severe hypertension and was not significant for women at 36 0 to
36 6 weeks. The induced group delivered, on average, 1.2 weeks earlier than
the control group and had a significantly lower rate of cesarean delivery (14
versus 19 percent). There were no significant differences between groups in
neonatal outcome.

This trial showed that preeclamptic women benefited from early intervention,
without incurring an increased risk of operative delivery or neonatal
morbidity. The trial was not large enough to determine whether small
differences in newborn outcomes or induction between 36 and 37 weeks
might be statistically significant. A follow-up economic analysis of this trial
concluded induction was also less costly overall than expectant management
with monitoring [ 17 ]. Another follow-up analysis showed that an
unfavorable cervix was not a reason to avoid induction [ 18 ].

The optimum management for women with mild preeclampsia and stable maternal and
fetal conditions at 34 0/7 to 36 0/7 weeks remains uncertain; no randomized trials have
been performed in this population [ 19 ]. These pregnancies are generally managed
expectantly to enable further fetal growth and maturation. Progression of the disease
is generally slow and observational data show that many patients with late onset
disease will reach term with only mild disease. For patients managed expectantly,
delivery is indicated as soon as they develop signs or symptoms of
severe preeclampsia/eclampsia ( table 2 ) or at 37 weeks of gestation if the disease
does not progress to this stage.

Prior to 34 0/7 weeks, guidelines from major medical organizations generally

recommend expectant management of mild preeclampsia, based on expert opinion,
given the high risk of complications of prematurity [ 4,19 ]. (See "Short-term
complications of the premature infant" and "Long-term complications of the premature
infant" and "Incidence and mortality of the premature infant" .)

EXPECTANT ANTEPARTUM MANAGEMENT OF MILD PREECLAMPSIA

Inpatient versus outpatient care Close maternal monitoring upon diagnosis of

preeclampsia is important to establish disease severity and the rate of progression.
Hospitalization is useful for making these assessments and facilitates rapid intervention
in the event of rapid progression. After the initial diagnostic evaluation, outpatient care
is a cost-effective option for women with stable mild preeclampsia [ 19-24 ].
Outpatient care can be provided in the patients home or, where available, at an
antenatal day care unit [ 25 ].

There are limited data on outcome of outpatient management of preeclamptic women.

An observational study and a randomized trial reported good outcomes, but these
studies had too few subjects to detect clinically significant differences in outcome
between inpatient and outpatient management [21,22 ]. A systematic review of three
trials with a total of 504 women with various complications of pregnancy observed no
major differences in clinical outcomes for mothers or babies between antenatal day
units or hospital admission [ 25 ].
Patients offered outpatient monitoring should be able to comply with frequent maternal
and fetal evaluations (every one to three days) and should have ready access to
medical care. Restricted activity is typically recommended since blood pressure is lower
in rested patients; however, there is no evidence that bedrest improves pregnancy
outcome [ 26 ]. Rest in the left lateral decubitus position can augment uteroplacental
flow, which may benefit some pregnancies. If signs or symptoms of disease
progression are noted, hospitalization for more intensive monitoring and possible
delivery is indicated.

Patients should be told to call their health care provider immediately if they develop
severe or persistent headache, visual changes, right upper quadrant or epigastric pain,
nausea or vomiting, shortness of breath, significant weight gain over one to two days,
or decreased urine output [ 27 ]. As with any pregnancy, decreased fetal movement,
vaginal bleeding, abdominal pain, rupture of membranes, or uterine contractions
should be reported immediately, as well.

Laboratory follow-up The minimum laboratory evaluation should include platelet

count, serum creatinine, and serum AST. These tests should be repeated once or twice
weekly in women with mild preeclampsia to assess for disease progression, and more
often if clinical signs and symptoms suggest worsening disease [ 27 ].

The value of other tests is less clearly defined. A rising hematocrit can be useful to look
for hemoconcentration, which suggests contraction of intravascular volume and
progression to more severe disease, while a falling hematocrit may be a sign of
hemolysis. An elevated serum indirect bilirubin concentration is a better sign of
hemolysis, although an elevated LDH may also be a marker of severe disease or HELLP
syndrome. Hemolysis can be confirmed by observation of schistocytes and helmet cells
on a blood smear ( picture 1A-B ). (See "HELLP syndrome" .)

Since several clinical studies have shown that neither the rate of increase nor the
amount of proteinuria affects maternal or perinatal outcome in the setting of
preeclampsia [ 5-8 ], repeated 24-hour urinary protein estimations are not useful once
the threshold of 300 mg/24 hours for the diagnosis of preeclampsia has been
exceeded. Serum creatinine alone can be used to monitor renal function. When
required, quantification of protein excretion can be performed using a 24-hour
collection or protein-to creatinine ratio on a random specimen. (See "Expectant
management of severe preeclampsia" .)

Treatment of hypertension The use of antihypertensive drugs to control mildly

elevated blood pressure in the setting of preeclampsia does not alter the course of the
disease or diminish perinatal morbidity or mortality, and should be avoided. The
indications for starting antihypertensive therapy, the choice of drug, and blood
pressure goals are discussed separately. (See "Management of hypertension in
pregnant and postpartum women", section on 'Preeclampsia' .)

Sodium restriction below the recommended daily intake and diuretics have no role in
routine therapy [ 28-30 ]. Although intravascular vascular volume is reduced, a
randomized trial showed that plasma volume expansion did not improve maternal or
fetal outcome [ 31 ].

Assessment of fetal well-being There are no data from randomized trials on

which to base recommendations for the optimal type and frequency of fetal biophysical
monitoring. We suggest daily fetal movement counts and twice weekly fetal nonstress
testing with assessment of amniotic fluid volume, or twice weekly biophysical profiles.
Testing is repeated immediately if there is an abrupt change in maternal condition.
(See "Antepartum fetal heart rate assessment" and "The fetal biophysical profile" .)

Evaluation of umbilical artery Doppler indices is also useful, as the results help in
optimal timing of delivery. In a meta-analysis of 16 randomized trials in high risk
pregnancies, knowledge of umbilical artery Doppler velocimetry results was associated
with a 29 percent reduction in perinatal death (RR 0.71, 95% CI 0.52-0.98, 10,225
babies, 1.2 versus 1.7 percent; number needed to treat 203, 95%CI 103- 4352),
primarily in pregnancies complicated by preeclampsia and/or growth restriction. The
frequency of assessment depends on the findings; weekly assessment is reasonable
when Doppler indices are normal. (See "Doppler ultrasound of the umbilical artery for
fetal surveillance", section on 'Clinical effectiveness' and "Doppler ultrasound of the
umbilical artery for fetal surveillance", section on 'Guidelines for clinical practice' .)

Assessment of fetal growth Early fetal growth restriction may be the first
manifestation of preeclampsia and is a criterion of severe disease. We suggest
sonographic estimation of fetal weight be performed to look for growth restriction and
oligohydramnios at the time of diagnosis of preeclampsia and then repeated every
three weeks if the initial examination is normal [ 27 ]. If fetal growth is suboptimal, the
frequency can be increased. (See "Fetal growth restriction: Evaluation and
management", section on 'Serial fetal weight assessment' and "Doppler ultrasound of
the umbilical artery for fetal surveillance" .)

Antenatal corticosteroids Although preeclampsia may accelerate fetal lung

maturation, neonatal respiratory distress remains common in premature neonates of
preeclamptic pregnancies [ 32,33 ]. Antenatal corticosteroids ( betamethasone ) to
promote fetal lung maturity should be administered to women less than 34 weeks of
gestation since they are at increased risk of progression to severe disease and preterm
delivery. (See "Antenatal corticosteroid therapy for reduction of neonatal morbidity and
mortality from preterm delivery" .)

INTRAPARTUM MANAGEMENT

Intrapartum monitoring Continuous maternal-fetal monitoring is indicated

intrapartum to identify worsening hypertension, deteriorating maternal hepatic, renal,
cardiopulmonary, neurological, or hematologic function, as well as abruptio placentae
or a nonreassuring fetal heart rate tracing. There are no evidence-based standards for
the optimal approach.

Fluids Fluid balance should be monitored closely to avoid excessive administration,

since women with severe disease are at risk of pulmonary edema and significant third-
spacing. Maintenance fluids of 80 mL/hour are often adequate in the absence of
ongoing fluid loss, such as bleeding. Oliguria that does not respond to a modest trial of
increased fluids should be tolerated. Diuretics are only indicated for treatment of
pulmonary edema.

Management of hypertension Severe hypertension is treated with

intravenous labetalol or hydralazine or oral nifedipine . (See "Management of
hypertension in pregnant and postpartum women", section on 'Acute therapy' .)

Anesthesia Neuraxial techniques are generally safe and effective in preeclamptic

women [ 34 ]. In preeclampsia, the two major anesthesia-related concerns with use of
neuraxial techniques are (1) the potential for a large drop in blood pressure due to
depleted intravascular volume and sympathetic blockade and (2) peridural hematoma
in women with severe thrombocytopenia. The former can be minimized by appropriate
adjustments in pre-hydration, drug choice, drug dosing, and drug delivery by the
anesthesiologist; however, a low platelet count may preclude neuraxial anesthesia.
(See"Adverse effects of neuraxial analgesia and anesthesia for obstetrics", section on
'Hypotension' and "Adverse effects of neuraxial analgesia and anesthesia for
obstetrics", section on 'Neuraxial analgesia and low platelets' .)

The major concerns associated with general anesthesia (for cesarean delivery) are a
transient spike in blood pressure during intubation (response to noxious stimuli),
hypotension (from reduction in cardiac output and systemic vascular resistance), and
difficult or failed intubation because of oropharyngeal edema. (See "Airway
management of pregnant women at delivery" .)

Given these issues, early patient assessment by the anesthesia team is desirable.

Invasive hemodynamic monitoring Invasive hemodynamic monitoring can be

useful in complicated patients, such as those with severe cardiac disease, severe renal
disease, severe oliguria, refractory hypertension, or pulmonary edema [ 1 ]. However,
most women can be managed without these tools and should not be exposed to the
risks associated with arterial and central venous catheterization. Randomized trials
have not been performed [ 35]. (See "Pulmonary artery catheterization: Indications
and complications" and "Complications of central venous catheters and their
prevention" .)

Seizure prophylaxis Based upon data from randomized trials, we administer

intrapartum magnesium sulfate seizure prophylaxis to women with mild or severe
preeclampsia. Although seizure and death are rare outcomes after non-treatment of
mild preeclampsia, we feel the benefit of treatment is justifiable given the low cost and
toxicity of magnesium sulfate and the relatively low number of patients that need to be
treated to prevent one seizure. In a randomized placebo-controlled trial including
10,000 women (MAGPIE [magnesium sulfate for prevention of eclampsia trial]), about
100 women with mild preeclampsia and about 60 women with severe preeclampsia
would need to be treated to prevent one seizure [ 36 ].

It is important to emphasize that seizure prophylaxis does not prevent progression of

disease unrelated to convulsions. Approximately 10 to 15 percent of women in labor
with mild preeclampsia will develop signs of severe preeclampsia (eg, severe
hypertension, severe headache, visual disturbance, epigastric pain, laboratory
abnormalities) or abruptio placenta, whether or not they receive magnesium therapy
[ 37,38 ].

We do not administer seizure prophylaxis to women with gestational hypertension

alone, as the seizure risk in the latter group is less than 0.1 percent [39 ].
(See "Gestational hypertension" .)

Magnesium sulfate versus other anticonvulsants Major medical organizations

worldwide consistently recommend magnesium sulfate as the drug of choice for the
prevention of eclampsia [ 1,19,40 ]. In randomized trials [ 36,41,42 ] and large
observational series [ 43 ], magnesium sulfate was more effective for prevention of a
first seizure than phenytoin [ 41 ] or an antihypertensive drug alone ( nimodipine )
[ 42 ] or placebo [ 43 ]. As an example, a trial that randomly assigned 2138
preeclamptic patients admitted to Labor and Delivery at Parkland Hospital to seizure
prophylaxis with magnesium sulfate or phenytoin reported eclamptic seizures in 10 of
1089 women assigned to phenytoin compared to none of 1049 women assigned to
magnesium sulfate [ 41 ]. Maternal and neonatal outcomes were similar in both
groups.

In meta-analyses of randomized trials in eclamptic women, magnesium sulfate was

safer and more effective for prevention of recurrent seizures
thanphenytoin , diazepam , or lytic cocktail (ie, chlorpromazine , promethazine , and
pethidine). These data provide additional indirect evidence of its effectiveness in
preeclampsia. (See "Eclampsia", section on 'Prevention of recurrent convulsions' .)

Magnesium regimen and monitoring There is no consensus on the optimal

magnesium regimen, when it should be started and terminated, or route of
administration [ 44 ]. The drug is usually initiated at the onset of labor or induction, or
prior to cesarean delivery [ 45,46 ]. It is usually not given to stable antepartum
patients off the labor unit, but is sometimes used in women with severe preeclampsia
being considered for expectant management. (See "Expectant management of severe
preeclampsia" .)

Dosing Although published dosage regimens for magnesium sulfate vary widely
(loading dose of 4 to 6 grams intravenously and maintenance dose of 1 to 3 grams per
hour), the most common regimen, and the one that we use, is a loading dose of 6
grams intravenously over 15 to 20 minutes followed by 2 grams per hour as a
continuous infusion [ 1,38,43,46 ]. An alternative regimen is 5 grams intramuscularly
into each buttock (total of 10 grams) followed by 5 grams intramuscularly every four
hours. However, this method is associated with more side effects, particularly pain at
the injection site.

There does not appear to be a clear threshold concentration for insuring the prevention
of convulsions, although a therapeutic range of 4.8 to 8.4 mg/dL(2.0 to
3.5 mmol/L) has been recommended based on retrospective data [ 47 ]. Loading doses
less than 6 grams are more likely to result in subtherapeutic magnesium levels (less
than 4.5 mg/dL) [ 43,48 ].
Since magnesium sulfate is excreted by the kidneys, dosing should be adjusted in
women with renal insufficiency (defined as a serum creatinine greater than
1.0 mg/dL). Such women should receive a standard loading dose (since their volume of
distribution is not altered), but a reduced maintenance dose (1 gram per hour or no
maintenance dose if the serum creatinine is greater than 2.5 mg/dL) and close
monitoring of their serum magnesium level every six hours.

The maintenance phase is given only if a patellar reflex is present (loss of reflexes
being the first manifestation of symptomatic hypermagnesemia), respirations exceed
12 per minute, and the urine output exceeds 100 mL per four hours. (See "Symptoms
of hypermagnesemia" .) Following serum magnesium levels is not required if the
woman's clinical status is closely monitored for evidence of potential magnesium
toxicity (see 'Complications and side effects' below). The maintenance dose should be
decreased if there is clinical evidence of magnesium toxicity.

Duration of therapy Magnesium sulfate is usually continued for 24 hours

postpartum [ 46 ]. Timing of drug discontinuation has been arbitrary; there are no high
quality data to guide therapy. In women who have only mild preeclampsia,
discontinuation of therapy after 12 hours may be safe [ 49 ]. In women with severe
preeclampsia or eclampsia, seizure prophylaxis is generally continued for 24 to 48
hours postpartum, after which the risk of recurrent seizures is low.

It is probably reasonable to extend the duration of magnesium sulfate therapy in

women whose disease has not begun to improve postpartum and shorten the duration
of therapy in women who are clearly improving clinically (eg, diuresis of
100 mL/hour for two consecutive hours, absence of symptoms [headache, visual
changes, epigastric pain], and absence of severe hypertension) [ 50-53 ]. Diuresis
(greater than 4 L/day) is believed to be the most accurate clinical indicator of
resolution of preeclampsia/eclampsia, but is not a guarantee against the development
of seizures [ 54 ]. In women with persistent renal impairment postpartum, it is
important to be cautious when administering a prolonged magnesium sulfate infusion
to prevent the occurrence of magnesium toxicity.

Complications and side effects Rapid infusion of magnesium sulfate causes

diaphoresis, flushing, and warmth, probably related to peripheral vasodilation and a
drop in blood pressure. Nausea, vomiting, headache, muscle weakness, visual
disturbances, and palpitations can also occur. Dyspnea or chest pain may be symptoms
of pulmonary edema, which is a rare side effect. (See "Symptoms of
hypermagnesemia" .)

Magnesium toxicity is uncommon in women with good renal function [ 55 ]. Toxicity is

related to serum magnesium concentration: loss of deep tendon reflexes occurs at 9.6
to 12.0 mg/dL (4.0 to 5.0 mmol/L), respiratory paralysis at 12.0 to 18.0 mg/dL (5 to
7.5 mmol/L), and cardiac arrest at 24 to 30mg/dL (10 to 12.5 mmol/L). Calcium
gluconate (1 gram intravenously over 5 to 10 minutes) should be administered only to
counteract life-threatening symptoms of magnesium toxicity (such as cardiorespiratory
compromise).
Magnesium sulfate is contraindicated in women with myasthenia gravis since it can
precipitate a severe myasthenic crisis (see "Management of myasthenia gravis in
pregnancy" ). Neuromuscular blockade and hypotension due to concurrent use of
magnesium sulfate and calcium channel blockers have been described in case reports,
but the risk appears to be minimal [ 56 ].

Although magnesium sulfate is a weak tocolytic, labor duration does not appear to be
affected by magnesium sulfate administration [ 57 ]. The risk of postpartum
hemorrhage, possibly related to uterine atony from magnesium's tocolytic effects, was
slightly increased in one trial [ 42 ].

Magnesium freely crosses the placenta; as a result, the cord blood concentration
approximates the maternal serum concentration. Maternal therapy causes a decrease
in baseline fetal heart rate, which generally remains within the normal range, and a
decrease in fetal heart rate variability, which may be absent or minimal [ 58 ].
Antenatal fetal assessment test results (eg, biophysical profile score and nonstress test
reactivity) are not significantly altered [ 59 ].

Magnesium therapy results in a transient reduction of total and ionized serum calcium
concentration due to rapid suppression of parathyroid hormone release [ 60 ]. Rarely,
hypocalcemia becomes symptomatic (myoclonus, delirium, ECG abnormalities).
(See "Symptoms of hypermagnesemia", section on 'Hypocalcemia' .) Cessation of
magnesium therapy will restore normal serum calcium levels. However, calcium
administration may be required if symptoms are present ( calcium gluconate 1 gram
intravenously over 5 to 10 minutes). (See "Causes and treatment of
hypermagnesemia" .)

Mechanism of anticonvulsant action The mechanism for the anticonvulsant

effects of magnesium sulfate has not been clearly defined. The primary effect is
thought to be central. Hypotheses include action at the n-methyl d-aspartate (NMDA)
receptor that raises the seizure threshold, membrane stabilization in the central
nervous system secondary to its actions as a non-specific calcium channel blocker, as
well as decreasing acetylcholine in motor nerve terminals [ 61,62 ]. Another theory is
that it promotes vasodilatation of constricted cerebral vessels by opposing calcium-
dependent arterial vasospasm, thereby reducing cerebral barotrauma [ 63 ].

POSTPARTUM MANAGEMENT Nonsteroidal antiinflammatory drugs (NSAIDs) for

pain control should be avoided in women with poorly controlled hypertension, oliguria,
renal insufficiency, or thrombocytopenia. (See "Nonselective NSAIDs: Overview of
adverse effects" .)

There are no evidence-based standards for the optimal approach to postpartum

monitoring and follow-up. We monitor vital signs every two hours while the patient
remains on magnesium sulfate and we repeat laboratory tests until two consecutive
sets of data are normal.

Severe hypertension should be treated; some patients will have to be discharged on

antihypertensive medications, which are discontinued when blood pressure returns to
normal. (See "Management of hypertension in pregnant and postpartum women",
section on 'Postpartum hypertension' .)

Patients should be followed closely as outpatients until complete resolution of

hypertension and laboratory abnormalities. Alternative diagnoses should be sought in
those with persistent abnormal findings after three to six months [ 64 ].
(See "Overview of hypertension in adults" .)

GUIDELINES FROM SELECTED ORGANIZATIONS A number of medical

organizations have published guidelines for management of preeclampsia. These
guidelines are generally consistent with the recommendations in this topic review.

American College of Obstetricians and Gynecologists (ACOG). Practice bulletin:

Diagnosis and management of preeclampsia and eclampsia [ 1 ]

National Institute for Health and Clinical Excellence (NICE). Hypertension in

pregnancy: The management of hypertensive disorders during pregnancy
[4]

Society of Obstetricians and Gynaecologists of Canada (SOGC). Diagnosis,

evaluation, and management of the hypertensive disorders of pregnancy
[ 19 ]

PROGNOSIS Prognostic issues include the risk of recurrent preeclampsia and

related complications in subsequent pregnancies and long-term maternal health risks.

Recurrence The recurrence risk varies with the severity and time of onset of the
acute episode [ 65 ]. Women with early onset, severe preeclampsia are at greatest risk
of recurrence (as high as 25 to 65 percent) [ 66-68 ]. The risk is much lower (5 to 7
percent) in women who had mild preeclampsia during the first pregnancy, versus less
than 1 percent in women who had a normotensive first pregnancy (does not apply to
abortions) [ 66,69-74 ]. The occurrence of preeclampsia in future pregnancies is best
illustrated by the following prospective study:

In a series of 125 women with severe second trimester preeclampsia followed

for five years, 65 percent developed recurrent preeclampsia and 35 percent
were normotensive in their subsequent pregnancy [ 66 ]. Of the preeclamptic
group, approximately one-third developed the disease at 27 weeks, one-
third at 28 to 36 weeks, and one-third at 37 weeks. Thus, 21 percent of
subsequent pregnancies were complicated by severe preeclampsia in the
second trimester.

Recurrent preeclampsia is more likely following a preeclamptic singleton pregnancy

than a preeclamptic twin pregnancy [ 75 ]. The recurrence risk in women with HELLP
syndrome (who may develop either HELLP or preeclampsia in a subsequent pregnancy)
is discussed separately. (See "HELLP syndrome" .)

Prevention Preventive therapy is reviewed elsewhere. (See "Prevention of

preeclampsia" .)
Risk of related obstetrical complications Preeclampsia, growth restriction,
preterm delivery, abruptio placentae, and stillbirth can all be sequelae of impaired
placental function. Women with pregnancies complicated by one of these disorders are
at increased risk of developing one of the other disorders in future pregnancies. Early
onset preeclampsia is more likely to be associated with one of these adverse events in
a subsequent pregnancy, even if normotensive, than late onset preeclampsia [ 76,77 ].

Long-term maternal risks

Cardiovascular disease Case-control and cohort studies consistently report that

preeclampsia is predictive of future cardiovascular and cerebrovascular disease. This
risk was summarized in two systematic reviews of controlled studies that evaluated the
risk of late cardiovascular events in women with and without a history of preeclampsia
[ 78,79 ]:

Compared with women with no history of the disease, women with

preeclampsia were at increased risk of developing hypertension (RR 3.70,
95% CI 2.70-5.05 at mean follow-up of 14 years), ischemic heart disease
(RR 2.16, 95% CI 1.86-2.52 at mean follow-up of 11.7 years), stroke (RR
1.81, 95% CI 1.45-2.27 at mean follow-up of 10.4 years), and venous
thromboembolism (RR 1.79, 95% CI 1.37-2.33 at mean follow-up of 4.7
years) [ 78 ]. The absolute risk that a woman with or without a history of
preeclampsia would develop one of these cardiovascular events at age 50 to
59 years was estimated to be 17.8 and 8.3 percent, respectively.

In addition, a graded relationship was observed between severity of

preeclampsia and risk of future cardiac disease (mild preeclampsia RR 2.00,
95% CI 1.83-2.19; moderate preeclampsia RR 2.99, 95% CI 2.51-3.58;
severe preeclampsia RR 5.36, 95% CI 3.96-7.27), as well as a correlation
between preeclampsia and future peripheral artery disease (RR 1.87, 95%
CI 0/94-3.73) [ 79 ]. The authors defined preeclampsia as 'mild' if the
pregnancy had an uncomplicated course, 'moderate' if preeclampsia was
complicated by fetal growth restriction or maternal seizures and 'severe' if
preeclampsia was complicated by preterm delivery or fetal demise.

A large prospective cohort study (Avon Longitudinal Study of Parents and Children,
ALSPAC) published after these reviews reported similar findings [ 80 ].

Women with early onset/severe preeclampsia with preterm delivery are at highest risk
of cardiovascular disease later in life, including during the premenopausal period
( table 3 ) [ 81 ]. In contrast, mild preeclampsia occurring late in gestation does not
appear to be associated with a high risk of remote cardiovascular disease [ 82 ]. The
stronger association between cardiovascular disease and preterm preeclampsia
suggests that the pathogenesis of early versus late preeclampsia may be different.

Several studies have demonstrated that women with a history of preeclampsia or

severe early onset fetal growth restriction exhibit impaired endothelial function and
vasodilatation remote from pregnancy [ 83-86 ]. Women with a history of hypertensive
disorders in pregnancy have higher levels of glucose, insulin, and unfavorable lipids
than women with a history of normotensive pregnancy [ 87 ]. Data from some
epidemiologic studies suggest that the increased risk of late cardiovascular morbidity in
previously preeclamptic women reflects an underlying predisposition in these women
for both disorders, but it is also possible that preeclampsia results in permanent
arterial changes leading to late cardiovascular disease [ 88-90 ]. Some investigators
have hypothesized that increased insulin resistance, sympathetic overactivity,
proinflammatory activity, endothelial dysfunction, and the abnormal lipid profile in
preeclamptic women constitute an early manifestation of metabolic syndrome and that
these changes persist after pregnancy, thereby putting affected woman at increased
risk of cardiovascular disease [ 91-94 ].

Diabetes mellitus In a large registry-based cohort study, gestational hypertension

or preeclampsia in a first pregnancy was associated with a three- to four-fold increase
in risk for subsequent development of type 2 diabetes mellitus compared with women
with no hypertensive disorder in pregnancy [ 95 ].

End-stage renal disease Women with preeclampsia may be at increased risk of

developing end-stage renal disease (ESRD) later in life, but the absolute risk is small.
A study that linked four decades of data from the Norwegian national birth and ESRD
registries found that women with preeclampsia in their first pregnancy had a four-fold
increase in risk of ESRD compared with women without preeclampsia (RR 4.7, 95% CI
3.6-6.1) after adjusting for known confounders, but the absolute risk of ESRD was less
than 1 percent within 20 years [ 96 ]. Similarly, a study using claims data from the
Taiwan National Health Insurance Program noted that women
with preeclampsia/eclampsia were at significantly higher risk of developing ESRD over
time than women without hypertensive disorders during pregnancy (incidence 5.33
versus 0.34 per 10,000 person-years) [ 97 ].

Although women who went on to develop ESRD may have had subclinical renal disease
during pregnancy, it is also possible that as yet undefined risk factors predisposed
these women to both preeclampsia and ESRD. It is less likely that preeclampsia
damages the kidney, thereby initiating a process of chronic deterioration.

Subclinical hypothyroidism A nested case-control study found that nulliparous

women who developed preeclampsia were twice as likely to develop subclinical
hypothyroidism during pregnancy and long after delivery than matched normotensive
controls [ 98 ]. The risk was strongest in women with recurrent preeclampsia and
without thyroid peroxidase antibodies, suggesting that an autoimmune mediated
mechanism of hypothyroidism was not involved. In a study including 25,000 pregnant
women, women with subclinical hypothyroidism identified during pregnancy were at
increased risk of developing severe preeclampsia compared with euthyroid women (OR
1.6, 95% CI 1.1-2.4), after adjustment for risk factors for preeclampsia [99 ].
Abnormal levels of thyroid hormones appear to damage endothelial cells, potentially
leading to preeclampsia and long-term cardiovascular sequelae.

Other A systematic review found no significant association between preeclampsia

and later development of cancer [ 78 ]. Observational studies from the United States,
Sweden, and Norway reported that women with preeclampsia were at reduced risk or
had no excess risk of cancer when followed 13 to 19 years postpartum [ 81,100-105 ].
In contrast, a study from Israel reported an increased risk of cancer in such women
(hazard ratio 1.27, 95% CI 1.03-1.57) with a median follow-up of 29 years
[ 106,107 ]. Site-specific increases were noted for cancer of the stomach, lung or
larynx, breast, and ovary. The discordant results may be explained by a number of
factors, including differences in patient populations, absence of or insufficient
adjustment for confounders, differences in length of follow-up, and incomplete
ascertainment.

INFORMATION FOR PATIENTS UpToDate offers two types of patient education

materials, The Basics and Beyond the Basics. The Basics patient education pieces
are written in plain language, at the 5 th to 6 th grade reading level, and they answer the
four or five key questions a patient might have about a given condition. These articles
are best for patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more sophisticated,
and more detailed. These articles are written at the 10 th to 12 th grade reading level
and are best for patients who want in-depth information and are comfortable with
some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage
you to print or e-mail these topics to your patients. (You can also locate patient
education articles on a variety of subjects by searching on patient info and the
keyword(s) of interest.)

Basics topics (see "Patient information: Preeclampsia (The Basics)" and "Patient
information: High blood pressure and pregnancy (The Basics)" and"Patient
information: HELLP syndrome (The Basics)" )

Beyond the Basics topics (see "Patient information: Preeclampsia (Beyond the
Basics)" )

SUMMARY AND RECOMMENDATIONS

The definitive treatment of preeclampsia is delivery to prevent development of

maternal or fetal complications from disease progression. Timing of delivery
is based upon gestational age, the severity of preeclampsia, and maternal
and fetal condition. (See 'Overview of management' above.)

Severe preeclampsia ( table 2 ) is generally regarded as an indication for

delivery, regardless of gestational age, given the high risk of serious maternal
morbidity. However, prolonged antepartum management in a tertiary care
setting or in consultation with a maternal-fetal medicine specialist is an
option for selected women remote from term (<34 weeks of gestation).
(See 'Severe preeclampsia' above.)

For women with mild preeclampsia, we suggest expectant management with

delivery at 37 weeks of gestation ( Grade 2B ). (See 'Mild
preeclampsia' above.)
 Expectant management of women with mild preeclampsia consists of frequent
laboratory monitoring (platelet count, liver and renal function tests),
assessment of maternal blood pressure and symptoms, and evaluation of
fetal growth and well-being. (See 'Expectant antepartum management of
mild preeclampsia' above.)

For women with preeclampsia between 23 and 34 weeks of gestation, we

recommend a course of antenatal glucocorticoids ( betamethasone ) (Grade
1A ). (See "Antenatal corticosteroid therapy for reduction of neonatal
morbidity and mortality from preterm delivery" .)

For women with severe preeclampsia, we recommend seizure prophylaxis

( Grade 1A ). The benefit of seizure prophylaxis is less clear in mild
preeclampsia; however, we suggest prophylaxis in these women ( Grade 2B ).
We recommend use of magnesium sulfate rather than phenytoin for seizure
prophylaxis ( Grade 1A ). (See 'Seizure prophylaxis' above.)

We give a loading dose of 6 grams magnesium sulfate intravenously over 15 to

20 minutes followed by 2 grams per hour as a continuous infusion. The
maintenance dose (but not the loading dose) should be adjusted in women
with renal insufficiency. (See 'Magnesium regimen and monitoring'above.)

Magnesium toxicity is related to serum concentration: loss of deep tendon

reflexes occurs at 8 to 10 mEq/L, respiratory paralysis at 10 to 15 mEq/L,and
cardiac arrest at 20 to 25 mEq/L. Calcium gluconate (1 gram intravenously
over 5 to 10 minutes) should be administered to counteract life-threatening
symptoms of magnesium toxicity. (See 'Complications and side
effects' above.)

There is an increased risk of preeclampsia recurrence in subsequent

pregnancies and possible long-term risks of cardiovascular disease.
(See'Prognosis' above.)