15/7/2019 Eclampsia - UpToDate

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Eclampsia
Author: Errol R Norwitz, MD, PhD, MBA
Section Editors: Charles J Lockwood, MD, MHCM, Steven C Schachter, MD
Deputy Editor: Vanessa A Barss, MD, FACOG

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jun 2019. | This topic last updated: Apr 08, 2019.

INTRODUCTION

Eclampsia refers to the occurrence of new-onset, generalized, tonic-clonic seizures or coma in a

woman with preeclampsia. It is the convulsive manifestation of preeclampsia and one of several
clinical manifestations at the severe end of the preeclampsia spectrum (table 1). Despite
advances in detection and management, preeclampsia/eclampsia remains a common cause of
maternal morbidity and death.

The clinical manifestations, diagnosis, and management of eclampsia will be reviewed here.
Issues related to preeclampsia are discussed separately:

● (See "Preeclampsia: Pathogenesis".)

● (See "Preeclampsia: Clinical features and diagnosis".)
● (See "Preeclampsia: Management and prognosis".)
● (See "Preeclampsia: Prevention".)
● (See "Expectant management of preterm preeclampsia with severe features".)

INCIDENCE AND EPIDEMIOLOGY

In high resource countries, the incidence of eclampsia is low and has been decreasing or stable at
1.5 to 10 cases per 10,000 deliveries [1-7]. In low and middle resource countries, however, the
incidence varies widely: from 19.6 per 10,000 deliveries in parts of Zambia to 142 per 10,000
deliveries in Sierra Leone [8].

Eclampsia occurs in 2 to 3 percent of women with preeclampsia with severe features (previously
called "severe" preeclampsia) who are not receiving anti-seizure prophylaxis, and in up to 0.6

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percent of women with preeclampsia without severe features (previously called "mild"
preeclampsia) [9].

Risk factors for eclampsia are similar to those for preeclampsia (table 2). Women at highest risk
are nonwhite, nulliparous, and from lower socioeconomic backgrounds. The peak incidence is in
adolescence and the early twenties, but incidence is also increased in women over age 35 [8].

PATHOGENESIS OF SEIZURES

The precise cause of eclamptic seizures is not clearly understood. Two models have been
proposed, based on the central role of hypertension. According to the first model, hypertension
causes a breakdown of the autoregulatory system of the cerebral circulation, leading to
hyperperfusion, endothelial dysfunction, and vasogenic and/or cytotoxic edema. In the second
model, hypertension causes activation of the autoregulatory system, leading to vasoconstriction of
cerebral vessels, hypoperfusion, localized ischemia, endothelial dysfunction, and vasogenic
and/or cytotoxic edema [10]. Cerebral inflammation may also play a role [11].

The pathogenesis of preeclampsia is reviewed elsewhere. (See "Preeclampsia: Pathogenesis".)

CLINICAL FINDINGS

Clinical presentation — Most women have premonitory signs/symptoms in the hours before the
initial seizure. In a systematic review including 59 studies involving over 21,000 women with
eclampsia from 26 countries, the most common antecedent signs/symptoms and percent of
women with the sign/symptom were [12]:

● Hypertension (75 percent)

● Headache (persistent frontal or occipital headaches or thunderclap headaches) (66 percent)

● Visual disturbances (scotomata, loss of vision [cortical blindness], blurred vision, diplopia,
visual field defects [eg, homonymous hemianopsia], photophobia) (27 percent)

● Right upper quadrant or epigastric pain (25 percent)

● Asymptomatic (25 percent)

Ankle clonus is also a common finding [13]. Altered mental status may be another premonitory
symptom.

Eclampsia is generally manifested by a generalized tonic-clonic seizure or coma. At onset, there is

an abrupt loss of consciousness, often associated with a scream or shriek. The muscles of the
arms, legs, chest, and back then become stiff. The woman may begin to appear cyanotic during

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this tonic phase. After approximately one minute, the muscles begin to jerk and twitch for an
additional one to two minutes. The tongue may be bitten; frothy and bloody sputum may come out
of the mouth.

The postictal phase begins once the twitching movements end. The woman is initially in a deep
sleep, breathing deeply, and then gradually wakes up, often complaining of a headache (table 3).
Most patients begin to recover responsiveness within 10 to 20 minutes after the generalized
convulsion. Focal neurologic deficits are generally absent.

Fetal bradycardia for at least three to five minutes is a common finding during and immediately
after the seizure. Resolution of maternal seizure activity is associated with fetal tachycardia and
loss of fetal heart rate variability, sometimes with transient decelerations [14]. The fetal heart rate
pattern generally improves with maternal and fetal therapeutic interventions (see 'Management'
below). A nonreassuring pattern with frequent, recurrent decelerations for more than 10 to 15
minutes despite maternal and fetal resuscitative interventions suggests the possibility of an occult
abruption [15].

On physical examination, neurologic findings may include memory deficits, brisk deep tendon
reflexes, visual perception deficits, visual processing deficits, altered mental status, and cranial
nerve deficits [16].

Timing — Eclampsia occurs preterm in approximately 50 percent of pregnancies and between 20

and 30 weeks of gestation in approximately 20 percent [1,17]. In the systematic review described
above, 59 percent of eclampsia occurred antepartum, 20 percent occurred intrapartum, and 21
percent occurred postpartum [12].

Approximately 90 percent of postpartum seizures occur within one week of delivery [18-22].
Antecedent symptoms are similar to those with antepartum and intrapartum eclampsia. In a series
of women discharged and later readmitted with eclampsia more than two days but less than six
weeks after delivery, the most common presenting symptom was headache, which occurred in
approximately 70 percent [22]. Other prodromal symptoms included shortness of breath, blurry
vision, nausea or vomiting, edema, neurological deficit, and epigastric pain. Of note, many women
did not have hypertension during the antecedent pregnancy.

Neuroimaging — Neuroimaging findings similar to those seen with reversible posterior

leukoencephalopathy syndrome (RPLS; also called posterior reversible encephalopathy syndrome
[PRES]) are found in over 90 percent of eclamptic patients in small series [23,24]. (See
"Reversible posterior leukoencephalopathy syndrome", section on 'Neuroimaging'.)

Neurohistopathology — A classic report from 1973 described neurohistopathology in eclamptic

women autopsied shortly after death [25]. In this series, >50 percent of women who died within
two days of seizures had cerebral hemorrhages. Petechial cortical hemorrhages were most
common, especially involving the occipital lobe. Diffuse cerebral edema and gross hemorrhage
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occurred less frequently. Cerebral venous thrombosis was common in women who developed
eclampsia postpartum.

A more contemporary series (2003 to 2006) of over 300 maternal deaths in Mozambique reported
the following types and frequencies of brain lesions: perivascular edema (68 percent), hemorrhage
(37 percent), hemosiderin (32 percent), parenchymal necrosis (16 percent), and small vessel
thrombosis (11 percent) [26]. Endothelial, histiocytic, and platelet markers suggested capillary
injury in the otherwise intact brain parenchyma, while stains for free radical formation were
positive mostly in areas of tissue injury, with focal positivity in intact glial/neuronal elements.

Electroencephalography — There is limited information on electroencephalography (EEG) in

eclampsia. A literature review reported postictal EEG abnormalities were common in eclamptic
women, and the EEG became normal with prolonged postpartum follow-up [27]. The studies were
of low methodologic quality and all but one were published between 1955 and 1984; findings using
modern equipment and practices have not been reported. (See "Electroencephalography (EEG) in
the diagnosis of seizures and epilepsy".)

DIAGNOSIS

Eclampsia is a clinical diagnosis based on the occurrence of new-onset tonic-clonic, focal, or

multifocal seizures in the absence of other causative conditions (eg, epilepsy, cerebral arterial
ischemia and infarction, intracranial hemorrhage, drug use), typically in a woman with a
hypertensive disorder of pregnancy (preeclampsia, gestational hypertension, HELLP syndrome)
[28].

Even if criteria for a hypertensive disorder of pregnancy are not met, the diagnosis can be made in
a pregnant woman with seizures who has the typical clinical and neuroimaging findings of
reversible posterior leukoencephalopathy syndrome (headache, confusion, visual symptoms,
vasogenic edema predominantly localized to the posterior cerebral hemispheres) [29,30]. (See
"Reversible posterior leukoencephalopathy syndrome".)

POSTICTAL EVALUATION

Women with preeclampsia who develop a generalized tonic-clonic seizure without persistent
neurologic deficit require no diagnostic evaluation beyond that for preeclampsia [31]. (See
"Preeclampsia: Clinical features and diagnosis".)

Atypical cases, such as women who do not meet criteria for diagnosis of preeclampsia (table 4),
gestational hypertension, or HELLP syndrome or who have persistent neurologic deficits,
prolonged loss of consciousness, onset of seizures >48 hours after delivery, onset of seizures
before 20 weeks of gestation, or seizures despite adequate magnesium sulfate therapy should be
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evaluated for other causes of seizures by a neurologist. A neuroimaging study should be

performed in these patients to evaluate for a culprit structural brain abnormality.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of new-onset seizures in a pregnant woman involves determining

whether the seizure was mostly incidental to the pregnant state (eg, brain tumor, ruptured
aneurysm), exacerbated by the pregnant state (eg, thrombotic thrombocytopenic purpura [TTP],
hemolytic uremic syndrome [HUS], cerebral venous thrombosis), or unique to the pregnant state
(eg, eclampsia). The following factors should be considered in differential diagnosis:

● The occurrence of preeclampsia/eclampsia before 20 weeks of gestation is rare and should

raise the possibility of an underlying molar pregnancy or a cause of seizure unrelated to
pregnancy. Molar pregnancy may be suspected based on the sonographic appearance of the
placenta and may occur with a coexistent normal co-twin. (See "Hydatidiform mole:
Epidemiology, clinical features, and diagnosis" and "Evaluation and management of the first
seizure in adults".)

● Persistent neurologic deficits suggest an anatomic abnormality, whether or not the woman
has eclampsia. Causes of sudden development of neurologic symptoms include stroke,
intracranial hemorrhage, brain mass lesion, toxic and metabolic encephalopathies, reversible
cerebral vasoconstriction syndrome, thrombotic thrombocytopenic purpura (TTP), and central
nervous system infection [32]. The assessment and differential diagnosis of a first seizure in
adults with neurologic deficits is described separately. (See "Evaluation and management of
the first seizure in adults".)

● Seizures without neurologic deficits may be triggered by metabolic abnormalities (eg,

hypocalcemia, hyponatremia, hypoglycemia), toxins (drug or alcohol withdrawal, drug
intoxication), infection (meningitis, encephalitis, sepsis), or recent head trauma. History,
physical examination, and laboratory studies can help distinguish these disorders from
eclampsia. Laboratory tests appropriate for the evaluation of a first seizure include
electrolytes, glucose, calcium, magnesium, hematology studies, renal function tests, liver
function tests, and toxicology screens, although the likelihood of finding a relevant
abnormality in unselected patients is low.

The absence of neurologic deficits does not exclude an anatomic abnormality within the brain.
Neuroimaging when the patient is clinically stable may be valuable in select cases. (See
"Evaluation and management of the first seizure in adults".)

● Pregnancy is a precipitating factor for some disorders associated with seizure activity, such as
TTP or hemolytic uremic syndrome (HUS). TTP and HUS may be indistinguishable from
eclampsia that occurs in a woman with HELLP syndrome (hemolysis, elevated liver enzymes,
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low platelets) (table 5) and approximately 10 to 20 percent of women with

preeclampsia/eclampsia have laboratory findings of HELLP syndrome. Eclampsia and HELLP
usually start to quickly improve after delivery, but delivery does not affect the course of TTP
and HUS. (See "HELLP syndrome", section on 'Differential diagnosis' and "Approach to the
patient with suspected TTP, HUS, or other thrombotic microangiopathy (TMA)".)

MANAGEMENT

Key principles — If the seizure is witnessed, maintaining airway patency and preventing
aspiration are the initial priorities. The woman should be rolled onto her left side. The immediate
issues include:

● Prevention of maternal hypoxia and trauma

● Treatment of severe hypertension, if present
● Prevention of recurrent seizures
● Evaluation for prompt delivery

Women who do not improve promptly following control of hypertension and seizures and those
who develop localizing neurologic signs should be evaluated by a neurologist.

Maternal oxygenation and protection from trauma — The patient is placed in a lateral position,
if possible. Supplemental oxygen (8 to 10 L/min) is administered via a nonrebreather face mask to
treat hypoxemia from hypoventilation during the seizure [15]. Raised, padded bedrails provide
protection from trauma.

Treatment of hypertension — Antihypertensive therapy (table 6) is administered to prevent

stroke, which accounts for 15 to 20 percent of deaths in women with eclampsia. A common
threshold for initiating antihypertensive therapy is sustained diastolic pressures greater than 105 to
110 mmHg or systolic blood pressures ≥160 mmHg, although the validity of these thresholds has
not been tested prospectively. The risk of stroke correlates with the degree of elevation in systolic
and diastolic pressures and maternal age [33], but it is not clear whether there is a threshold
pressure above which therapy should be started in pregnant hypertensive women [34]. The
cerebral vasculature of women with underlying chronic hypertension can probably tolerate higher
systolic pressures without injury, while adolescents with normally low blood pressures may benefit
from starting treatment at lower blood pressure levels.

The indications for treatment of hypertension, drug choice and dose, and target blood pressure
are the same as in preeclampsia and reviewed in detail separately. (See "Management of
hypertension in pregnant and postpartum women", section on 'Treatment of hypertension in
preeclampsia'.)

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Prevention of recurrent seizures — The anticonvulsive drug of choice is magnesium sulfate.

Treatment is primarily directed at prevention of recurrent seizures rather than control of the initial
seizure since the initial seizure is usually of short duration and may occur in a setting where
intravenous (IV) access and drugs are not readily available.

Approximately 10 percent of women with eclampsia will have repeated seizures if managed
expectantly [35]. There is universal agreement that women with eclampsia require anticonvulsant
therapy to prevent recurrent seizures and the possible complications of repeated seizure activity:
neuronal death, rhabdomyolysis, metabolic acidosis, aspiration pneumonitis, neurogenic
pulmonary edema, and respiratory failure. Magnesium sulfate is the drug of choice based on
randomized trials demonstrating that it reduces the rate of recurrent seizures by one-half to two-
thirds (relative risk [RR] 0.44, 95% CI 0.32-0.51) and the rate of maternal death by one-third (RR
0.62, 95% CI 0.39-0.99) [9].

A series of systematic reviews reported magnesium sulfate was safer and more effective than
phenytoin, diazepam, or lytic cocktail (ie, chlorpromazine, promethazine and pethidine) for
prevention of recurrent seizures in eclampsia [36-38]. Additional advantages of magnesium sulfate
therapy were its low cost, ease of administration (eg, cardiac monitoring is unnecessary), and lack
of sedation. An additional benefit is that in utero exposure to magnesium sulfate therapy
decreases the risk of cerebral palsy and severe motor dysfunction in offspring born prematurely.
(See "Neuroprotective effects of in utero exposure to magnesium sulfate".)

The Eclampsia Trial Collaborative Group conducted the seminal trial establishing the effectiveness
of magnesium sulfate therapy in eclampsia [39]. In two international multicenter trials, 905 women
with eclampsia were randomly assigned to receive either magnesium sulfate or diazepam and
another 775 women with eclampsia were randomly assigned to receive either magnesium sulfate
or phenytoin. The primary outcome measures were rates of recurrent seizures and maternal
death. Magnesium sulfate was significantly more effective than either diazepam or phenytoin:

● Women allocated to magnesium sulfate therapy had one-half the rate of recurrent seizures of
those allocated to diazepam (13 and 28 percent, respectively). There were no other
significant differences in maternal or perinatal mortality and/or morbidity between the two
groups.

● Women allocated to magnesium sulfate therapy had one-third the rate of recurrent seizures of
those allocated to phenytoin (6 versus 17 percent). In this arm of the study, the magnesium
sulfate group was less likely to be admitted to an intensive care facility (17 versus 25
percent), less likely to require ventilatory support (15 versus 23 percent), and less likely to
develop pneumonia (4 versus 9 percent) compared with the phenytoin group. There were no
other significant differences in maternal mortality or perinatal outcome between the two
groups.

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Administration of magnesium sulfate

● Loading dose – We administer a loading dose of magnesium sulfate 6 g IV over 15 to 20

minutes. This dose quickly and consistently achieves a therapeutic level. Loading doses of 4
to 6 g IV are commonly used [9]. An alternative dose/route is magnesium sulfate 5 g
intramuscularly into each buttock for a total of 10 g; however, the onset of a therapeutic effect
will be slower and intramuscular injection is painful. These loading doses may be given safely
to patients with renal insufficiency.

● Maintenance dose – We administer a maintenance dose of magnesium sulfate 2 g/hour as a

continuous IV infusion to women with good renal function. Maintenance doses of 1 to 3 g/hour
are commonly used. Alternatively, magnesium sulfate 5 g can be given intramuscularly every
four hours; a lower dose maintenance regimen (2.5 g intramuscularly every four hours) may
also be effective and more cost effective in low resource areas [40-42]. The maintenance
phase is given only if a patellar reflex is present (loss of deep tendon reflexes is the first
manifestation of symptomatic hypermagnesemia), respirations are greater than 12 per
minute, and urine output is >100 mL over four hours. Following serum magnesium levels is
not required in women with good renal function if the woman's clinical status is closely
monitored and shows no evidence of potential magnesium toxicity.

In patients with renal insufficiency, maintenance dosing should be lower and dosed in
consultation with a nephrologist or pharmacologist and magnesium levels should be
monitored. The author generally holds the maintenance infusion if the serum creatinine is
>1.5 mg/dL (133 micromol/L) or if the urine output is <20 mL per hour and rechecks the
magnesium level in six hours. If the serum creatinine is 1.0 to 1.5 mg/dL (88 to 133
micromol/L) and the urine output is adequate, the maintenance infusion is reduced by half to
1 g /hour and a magnesium level is rechecked in six hours.

A clear threshold magnesium concentration for insuring the prevention of seizures has not been
established, but a range of 4.8 to 8.4 mg/dL (1.9 to 3.5 mmol/L) is recommended if serum levels
are checked because of recurrent seizures or concerns about toxicity [43]. The dose should be
adjusted according to the clinical response of individual patients.

Calcium gluconate (1 g IV) may be administered to counteract magnesium toxicity, if necessary.

Concurrent use of magnesium sulfate with calcium channel blockers may result in hypotension,
but the risk appears to be minimal. Magnesium sulfate is contraindicated in women with
myasthenia gravis since it can precipitate a severe myasthenic crisis.

Additional information on complications and side effects of magnesium sulfate therapy, dosing,
and possible mechanisms of action can be found separately. (See "Preeclampsia: Management
and prognosis", section on 'Toxicity' and "Preeclampsia: Management and prognosis", section on

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'Dosing' and "Preeclampsia: Management and prognosis", section on 'Drug of choice: Magnesium
sulfate'.)

Response to therapy — Women who do not improve within 10 to 20 minutes following control of
hypertension and seizures and those with neurologic deficits should be evaluated by a neurologist
as they may have ongoing nonconvulsive seizures or underlying structural pathology, such as
hemorrhage. (See "Evaluation and management of the first seizure in adults".)

There is no role for mannitol in the routine care of women with eclampsia [44]. It can be harmful
because it can enter the brain through a damaged blood-brain barrier and reverse the osmotic
gradient, thus increasing intracranial pressure. A neurologist should be consulted for management
of women with signs/symptoms potentially related to increased intracranial pressure (eg,
depressed consciousness, papilledema, respiratory depression). (See "Evaluation and
management of elevated intracranial pressure in adults".)

Management of recurrent seizures — Recurrent seizures in patients on maintenance

magnesium sulfate therapy can be treated with an additional bolus of 2 to 4 g magnesium sulfate
administered IV over five minutes, with frequent monitoring for signs of magnesium toxicity (eg,
loss of patellar reflex, respirations <12 per minute) [11,39,45]. In cases refractory to magnesium
sulfate (patient is still seizing at 20 minutes after the bolus or more than two recurrences), a health
care provider can administer sodium amobarbital (250 mg IV over three minutes), thiopental, or
phenytoin (1250 mg IV at a rate of 50 mg/minute) [28]. Endotracheal intubation and assisted
ventilation in the intensive care unit are appropriate in these circumstances.

Status epilepticus, as well as recurrent seizures while on magnesium seizure prophylaxis, should
raise concerns about an intracranial lesion/stroke. Although neurology consultation and head
imaging are indicated in this setting, the acute management of the seizures is similar regardless of
the cause of status epilepticus. (See "Convulsive status epilepticus in adults: Treatment and
prognosis".)

Fetal resuscitation — Fetal bradycardia lasting at least three to five minutes is a common finding
during and immediately after an eclamptic seizure and does not necessitate emergency cesarean
delivery. Stabilizing the mother by administering antiseizure drugs and oxygen and treating severe
hypertension (if present) can help the fetus recover in utero from the effects of maternal hypoxia,
hypercarbia, and uterine tachysystole. However, if the fetal heart rate tracing does not improve
within 10 to 15 minutes despite maternal and fetal resuscitative interventions, then the possibility
of an occult abruption should be considered and emergency delivery may be indicated [15].

Delivery — Eclampsia is usually considered an absolute contraindication to expectant

management, although this has been attempted [46]. The definitive treatment for eclampsia is
prompt delivery; however, this does not necessarily preclude induction and a trial of labor [28,47].

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After maternal stabilization, factors to consider in determining the mode of delivery are gestational
age, cervical status, whether the patient is in labor, and fetal condition and position.

We believe that induction is a reasonable option for pregnancies at least 32 to 34 weeks of

gestation, and for earlier gestations with a favorable Bishop score (table 7). Cervical ripening
agents can be used to improve the Bishop score; however, in our opinion, long inductions should
be avoided and a clear endpoint for delivery planned (eg, within 24 hours). In a trial that randomly
assigned 200 rural Indian women at ≥34 weeks with eclampsia to cesarean delivery or induction
after initial stabilization, planned cesarean delivery did not significantly reduce the rate of adverse
maternal or fetal outcomes, and almost three-quarters of women in the planned vaginal delivery
group succeeded in delivering vaginally [48]. This trial provides support for induction of labor,
although it had several limitations: the number of adverse events was small, leading to wide
confidence intervals, and the population was not representative of women and intrapartum care in
higher resource settings.

In contrast, we would not induce women with eclampsia who are less than 32 to 34 weeks of
gestation and have an unfavorable cervix. In United States studies, less than one-third of women
with severe preeclampsia/eclampsia remote from term successfully delivered vaginally after
induction of labor [35,49,50]. Cesarean delivery is a reasonable option for these women. Because
the fetus benefits from in utero resuscitation before delivery, we wait 15 to 20 minutes and until the
mother and fetus show signs of recovery (control of seizures; mother oriented to name, time, and
place; fetal heart rate reassuring) before proceeding to surgery, if possible.

Anesthesia — Anesthesia issues are the same as for women with preeclampsia. (See
"Preeclampsia: Management and prognosis", section on 'Analgesia and anesthesia'.)

POSTPARTUM CARE

The postpartum care of women with eclampsia is described below, and not altered because of
neuroimaging findings consistent with reversible posterior leukoencephalopathy syndrome (RPLS;
also called posterior reversible encephalopathy syndrome [PRES]).

Duration of magnesium sulfate therapy — Seizures due to eclampsia always resolve

postpartum, generally within a few hours to days. 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 [51].

The optimal duration of magnesium sulfate therapy has not been determined. When begun before
delivery, we continue magnesium sulfate for 24 to 48 hours postpartum, at which time the risk of
recurrent seizures is low. When begun for postpartum eclampsia, we maintain therapy for 24 to 48
hours. In either case, therapy is continued in women in whom signs and symptoms of
preeclampsia have not started to improve and discontinued in women who are clearly improving
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clinically (eg, diuresis of ≥100 mL/hour for two consecutive hours and the absence of symptoms).
Decisions regarding maternal activity, oral intake, and infant care while on magnesium sulfate
therapy should be made on a case-by-case basis.

Treatment of postpartum hypertension — Antihypertensive therapy is administered to prevent

stroke. Medications similar to those used before delivery (table 6) are often used postpartum,
since most are compatible with breastfeeding. Target blood pressure is also the same. (See
"Management of hypertension in pregnant and postpartum women", section on 'Choice of drug
and dose' and "Management of hypertension in pregnant and postpartum women", section on
'Target blood pressure'.)

If prepregnancy blood pressure was normal and the patient is not hypertensive on medication, it is
reasonable to stop the antihypertensive agent after three weeks and monitor blood pressure to
assess whether further treatment is indicated. (See "Management of hypertension in pregnant and
postpartum women", section on 'Postpartum hypertension'.)

Driving — Many health care professionals caring for women with peripartum seizures have not
considered issues relating to fitness to drive after an eclamptic seizure [52]. States vary widely in
driver-licensing requirements for patients with seizures and in the responsibilities of physicians to
notify state authorities. Most, but not all, specify a mandatory seizure-free interval prior to
licensure and driving. Some licensing bureaus include mention of mitigating factors such as an
acute symptomatic seizure, but most do not. This topic is discussed in detail elsewhere. (See
"Driving restrictions for patients with seizures and epilepsy", section on 'Acute symptomatic
seizure'.)

Neurology follow-up — Atypical cases, such as women who do not meet criteria for diagnosis of
preeclampsia (table 4), gestational hypertension, or HELLP syndrome or who have persistent
neurologic deficits, prolonged loss of consciousness, onset of seizures >48 hours after delivery,
onset of seizures before 20 weeks of gestation, or seizures despite adequate magnesium sulfate
therapy, should have follow-up with a neurologist.

PREGNANCY OUTCOME

Maternal — Maternal complications occur in up to 70 percent of women with eclampsia. The

types and frequencies of complications from one review are summarized in the table (table 8).
Additional complications include intracerebral hemorrhage, transient blindness, and
cardiorespiratory arrest [35]. Hepatocellular damage, renal dysfunction, coagulopathy,
hypertension, and neurologic abnormalities typically resolve in the hours and days following
delivery. However, brain damage from hemorrhage or ischemia may result in permanent
neurologic sequelae and is the most common cause of death in eclamptic women [53,54].

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Maternal mortality rates of 0 to 14 percent have been reported over the past few decades
[1,6,8,55-57]. Maternal mortality and severe morbidity rates are lowest among women receiving
regular prenatal care who are managed by experienced physicians in tertiary centers (maternal
mortality 0 to 1.8 percent) [15,35,55,58-60]. The highest mortality rates are in low-resource
countries where prenatal, intrapartum, and neonatal care are compromised by the limited
resources [8,57,61]. These relationships are illustrated by the following large series:

● A population-based cohort study from Canada including 1481 cases of eclampsia from 2003
to 2009 reported a case mortality rate of 0.34 percent (5/1481) [3]. Severe morbidity included
need for assisted ventilation (53 percent), blood transfusion (24 percent), cardiac failure (10
percent), acute renal failure (9 percent), embolism (5 percent), sepsis (5 percent), adult
respiratory distress syndrome (5 percent), and shock (4 percent).

● A prospective study including nearly 2700 women with eclampsia in low and middle resource
countries reported maternal mortality in 6.9 percent [8]. The case fatality rate ranged from 2.1
percent (5/242) in a part of Zambia to 14.4 percent (18/125) in Haiti.

Fetal and neonatal — Premature delivery, abruptio placentae, and intrauterine asphyxia are the
primary causes of perinatal death in eclamptic pregnancies. A population-based cohort study from
Canada reported fetal death rates in eclamptic and noneclamptic pregnancies of 10.8 and 4.1 per
1000 total births, respectively; neonatal death rates were 7.5 and 2.2 per 1000 live births,
respectively [3]. A study from low and middle resource countries reported that the overall rate of
stillbirth or neonatal mortality in women with eclampsia varied from 41 per 1000 in Malawi to 231
per 1000 in a part of Uganda [8].

Eclamptic pregnancies had a five- to sevenfold increased risk of preterm birth, which likely
accounted for the higher neonatal mortality and high neonatal morbidity (73 percent had
respiratory distress syndrome). Twenty-one percent of infants were small for gestational age.

LONG-TERM PROGNOSIS

Recurrence risk — Recurrent eclampsia occurs in 2 percent of subsequent pregnancies [62,63].

The risk appears to be reduced by close maternal monitoring and timely intervention if
preeclampsia develops [64]. Preeclampsia, however, cannot be prevented in most cases. (See
"Preeclampsia: Prevention".)

The risk of recurrence was illustrated by a study that followed 159 nulliparous women with a
history of eclampsia and no preexisting hypertension through 334 subsequent pregnancies [65].
The incidence of preeclampsia without severe features, preeclampsia with severe features, and
eclampsia in these pregnancies was 13, 9, and 2 percent, respectively. The risk for preeclampsia
but not eclampsia was higher for the subset of women whose eclampsia occurred at ≤30 weeks of

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gestation in the index pregnancy. In these women, preeclampsia without severe features,
preeclampsia with severe features, and eclampsia occurred in 17, 25, and 2 percent, respectively.

Outcome of future pregnancies — In addition to preeclampsia/eclampsia, women with a history

of severe preeclampsia/eclampsia are at increased risk of obstetric complications in subsequent
pregnancies compared with women with no such history. These problems include [62,63,65,66]:

● Abruptio placentae (2.5 to 6.5 versus 0.4 to 1.3 percent of the general obstetrical population)
● Preterm delivery (15 to 21 versus 12 percent)
● Intrauterine growth restriction (12 to 23 versus 10 percent)
● Perinatal mortality (4.6 to 16.5 versus 1 percent)

Women with a history of preeclampsia/eclampsia remote from term (less than 28 weeks of
gestation) are at highest risk of developing these complications as well as recurrent
preeclampsia/eclampsia [65,66]. This risk appears to be the same whether they had preeclampsia
with severe features or eclampsia.

Long-term maternal health — Chronic hypertension develops in 0 to 78 percent (mean 24

percent) of women with a history of preeclampsia/eclampsia [62,63,65-67]. The wide range
reported in the literature is due to factors such as differences in maternal age and duration of
follow-up (the increased risk of subsequent hypertension only becomes apparent after an average
follow-up of 10 years [63]). The risk appears to be highest in the subgroup of women who have
subsequent pregnancies complicated by hypertension, multiparas with eclampsia, and women
with eclampsia remote from term [62,63,65].

In a study of 39 women with a history of eclampsia, magnetic resonance imaging performed an

average of 6.4 years following the index pregnancy revealed that these women had a higher
prevalence of white matter lesions than matched controls with normotensive uncomplicated
pregnancies (odds ratio [OR] 3.3, 95% CI 1.05-10.6) [68]. Approximately 15 percent of women in
each group were currently hypertensive or on antihypertensive therapy. The source and
significance of these lesions are unclear; affected women do not appear to have increased
functional impairment as may be seen in other patients with white matter lesions. A study of
eclamptic women reported no objective cognitive impairment as compared with controls when
evaluated 2 to 20 years after delivery [69].

Women with eclampsia may be at higher risk of a future seizure, but the absolute risk is small. In a
retrospective study that included 1615 women with eclampsia, the adjusted hazard ratio for future
seizures was 5.4 (95% CI 2.4-12.1), and the absolute risk was one seizure per 2200 person years
[70]. The authors did not distinguish women who had one subsequent seizure from those who had
recurrent seizures.

Both preeclamptic and eclamptic women are at increased risk of developing cardiovascular and
cerebrovascular disease and diabetes later in life. These data are discussed elsewhere. (See
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"Preeclampsia: Management and prognosis", section on 'Prognosis'.)

CAN ECLAMPSIA BE PREDICTED AND PREVENTED?

In women who have been diagnosed with preeclampsia, prophylactic administration of magnesium
sulfate can usually prevent seizures (see "Preeclampsia: Management and prognosis", section on
'Seizure prophylaxis'). In one review of 179 consecutive cases of eclampsia, factors identified to
be at least partially responsible for failure to prevent seizures were: physician error (36 percent),
lack of prenatal care (19 percent), abrupt onset (18 percent), magnesium failure (13 percent), late
postpartum onset (12 percent), and early onset before 21 weeks (3 percent) [71].

The majority of eclamptic women have one or more antecedent symptoms in the hours prior to an
eclamptic seizure, thus pregnant women should be counseled to call their health care provider if
these symptoms develop (see 'Clinical findings' above). However, up to 40 percent of eclamptic
seizures are not preceded by premonitory signs and symptoms [1,71-74].

The relationship between hypertension, signs and symptoms of cortical irritability (eg, headache
that is usually severe or persistent, visual disturbances, nausea, vomiting, fever, hyperreflexia)
and seizures remains unclear. The magnitude of blood pressure elevation does not appear to be
predictive of eclampsia, although it correlates well with the incidence of stroke (figure 1). Twenty to
38 percent of eclamptic patients have a maximal blood pressure less than 140/90 prior to their
seizure and approximately 20 percent have no evidence of proteinuria [1,56,58]. While
antihypertensive treatment is recommended in women with blood pressures ≥160/105 to 110
mmHg, the use of antihypertensive drugs to control mildly elevated blood pressure in the setting of
preeclampsia/eclampsia does not alter the course of the disease or diminish perinatal morbidity or
mortality. Pharmacologic treatment of mild hypertension is not recommended, as neither maternal
nor fetal benefits have been demonstrated. (See "Management of hypertension in pregnant and
postpartum women".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Hypertensive disorders of
pregnancy".)

SUMMARY AND RECOMMENDATIONS

● Eclampsia is a clinical diagnosis based on the occurrence of new-onset tonic-clonic, focal, or

multifocal seizures in the absence of other causative conditions (eg, epilepsy, cerebral arterial
ischemia and infarction, intracranial hemorrhage, drug use) in a woman with a hypertensive
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disorder of pregnancy (preeclampsia, gestational hypertension, HELLP syndrome. (See

'Diagnosis' above.)

● An eclamptic seizure occurs in 2 to 3 percent of women with severe features of preeclampsia

who are not receiving anti-seizure prophylaxis and between 0 and 0.6 percent in women with
preeclampsia without severe features. (See 'Incidence and epidemiology' above.)

● Most women have premonitory signs/symptoms in the hours before their initial seizure, such
as hypertension and proteinuria, headache, visual disturbances, and/or right upper quadrant
or epigastric pain. (See 'Clinical findings' above.)

● Eclampsia occurs before term in approximately 50 percent of women. Thirty-eight to 55

percent of eclampsia occurs antepartum, 13 to 36 percent occurs intrapartum, 5 to 39 percent
occurs ≤48 hours postpartum, and 5 to 17 percent occurs >48 hours postpartum.
Approximately 90 percent of postpartum seizures occur within one week of delivery. (See
'Clinical findings' above.)

● Fetal bradycardia lasting at least three to five minutes is a common finding during and
immediately after an eclamptic seizure. Emergent cesarean delivery is not needed unless the
fetal heart rate tracing does not improve within 10 to 15 minutes of maternal and fetal
resuscitative interventions. (See 'Fetal resuscitation' above.)

● Key management issues are: prevention of maternal hypoxia and trauma, treatment of severe
hypertension (if present), prevention of recurrent seizures with magnesium sulfate, and
evaluation for prompt delivery. (See 'Key principles' above.)

● For women with eclampsia, we recommend treatment with magnesium sulfate rather than
other anticonvulsants (Grade 1A). Compared with phenytoin and diazepam, magnesium
sulfate reduces the rate of recurrent seizures by one-half to two-thirds and reduces the rate of
maternal death by one-third. (See 'Prevention of recurrent seizures' above.)

● We suggest using an intravascular magnesium sulfate regimen rather than an intramuscular

regimen (Grade 2C). We use a 6 gram loading dose over 15 to 20 minutes, followed by 2
grams/hour as a continuous intravenous infusion. Loading doses of 4 or 5 grams are also
reasonable and a lower or higher maintenance dose (1 or 3 g/hour) is sometimes required.

The maintenance phase is given only if a patellar reflex is present (loss of deep tendon
reflexes is the first manifestation of symptomatic hypermagnesemia), respirations are greater
than 12 per minute, and urine output is over 100 mL in four hours.

The loading dose may be given safely in renal insufficiency, but the maintenance dose in
these patients should be omitted or reduced in consultation with a nephrologist or
pharmacologist. Magnesium levels should be monitored in patients with renal insufficiency.
(See 'Administration of magnesium sulfate' above.)
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● A common threshold for initiating antihypertensive therapy is sustained diastolic pressures

greater than 105 to 110 mmHg or systolic blood pressures ≥160 mmHg. (See 'Treatment of
hypertension' above.)

● Delivery is the only curative treatment, but this does not preclude induction of labor. Cesarean
delivery is a reasonable option for women less than 32 to 34 weeks of gestation with an
unfavorable cervix. After a seizure, in the absence of fetal bradycardia, we suggest waiting 15
to 20 minutes and until the mother and fetus show signs of recovery (control of seizures;
mother oriented to name, time, and place; fetal heart rate reassuring) before proceeding to
surgery, if possible. (See 'Delivery' above.)

● Seizures due to eclampsia always resolve in the postpartum period, generally within a few
hours to days. 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. When begun before delivery, we continue magnesium sulfate for 24
to 48 hours postpartum. When begun for postpartum eclampsia, we maintain therapy for 24 to
48 hours. (See 'Duration of magnesium sulfate therapy' above.)

● The risk of recurrent eclampsia in a future pregnancy is 2 percent. (See 'Recurrence risk'
above.)

● In addition to preeclampsia/eclampsia, women with a history of severe

preeclampsia/eclampsia are at increased risk of obstetric complications in subsequent
pregnancies. They are also at increased risk of cardiovascular disease, cerebrovascular
disease, and diabetes later in life. (See 'Long-term maternal health' above.)

● Eclampsia may not be preventable when of abrupt onset, onset early in pregnancy, or onset
after postpartum hospital discharge. (See 'Can eclampsia be predicted and prevented?'
above.)

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