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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: Apr 2024.

This topic last updated: Feb 05, 2024.

INTRODUCTION

Eclampsia refers to the occurrence of new-onset, generalized, tonic-clonic seizures or coma in a patient with preeclampsia or gestational hypertension
(in those cases where, in retrospect, a diagnosis of gestational hypertension was given before the patient went on to meet criteria for
preeclampsia/eclampsia). (See "Gestational hypertension".)

Eclampsia 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,
especially in resource-limited areas.

The clinical manifestations, diagnosis, and management of eclampsia will be reviewed here. Issues related to preeclampsia and HELLP (hemolysis,
elevated liver enzymes, low platelets) syndrome are discussed separately:

● (See "Preeclampsia: Pathogenesis".)

● (See "Preeclampsia: Clinical features and diagnosis".)
● (See "Preeclampsia: Antepartum management and timing of delivery".)
● (See "Preeclampsia: Prevention".)
● (See "Preeclampsia with severe features: Delaying delivery in pregnancies remote from term".)
● (See "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)".)

EPIDEMIOLOGY

High-resource countries have a low incidence of eclampsia and the incidence has been 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].

In one review of patients who did not receive magnesium sulfate antiseizure prophylaxis, eclampsia occurred in 2 to 3 percent of those with
preeclampsia with severe features (previously called "severe" preeclampsia) and in 0 to 0.6 percent of those with preeclampsia without severe features
(previously called "mild" preeclampsia), but data were limited [9].

Risk factors for eclampsia are similar to those for preeclampsia ( table 2). The peak incidence is in adolescence and the early twenties age group, but
the incidence is also increased after age 35 years [8].

PATHOGENESIS OF SEIZURES

The precise cause of eclamptic seizures is not clearly understood. Two models have been proposed, based on the effect of hypertension on the
vasculature of the brain. 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. This is typical of a barotrauma injury. In the second model,
hypertension causes activation of the autoregulatory system, leading to constriction 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 — Eclampsia occurs most often in patients with known preeclampsia, but may sometimes be the presenting feature of the
disorder. Most patients have premonitory signs/symptoms in the minutes or hours before the initial seizure. In a systematic review including 59 studies
involving over 21,000 patients with eclampsia from 26 countries, the most common antecedent signs/symptoms and percent of patients with the
signs/symptoms 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)

On physical examination, neurologic findings may include brisk deep tendon reflexes (clonus), deficits in visual perception and processing, altered
mental status/memory deficits, and cranial nerve deficits [13,14].

Characteristics of eclamptic seizures — Eclampsia is generally manifested by a self-limited generalized tonic-clonic seizure. The initial tonic phase is
characterized by an abrupt loss of consciousness and stiffening of the muscles of the arms, legs, chest, and back. The patient may begin to appear
cyanotic. After approximately one minute, the clonic phase begins as 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 seizure typically resolves spontaneously within a few minutes. Other
manifestations include focal or multifocal seizures or coma, but these are less common.

The postictal phase begins once the twitching movements end. The patient initially appears as if sleeping, breathing deeply, and then gradually
regaining consciousness, 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 response to eclampsia — 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
[15]. The fetal heart rate pattern generally improves with maternal and fetal therapeutic interventions. 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 [16].
(See 'Management' below and 'Fetal resuscitation' below.)

Time of presentation

● Approximately 50 percent of eclampsia cases occur preterm and approximately 20 percent occur between 20 and 30 weeks of gestation [1,17].

● Approximately 60 percent of eclampsia cases occur antepartum, 20 percent occur intrapartum, and 20 percent occur postpartum [12].

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

Neuroimaging — In over 90 percent of patients with eclampsia in small series, neuroimaging findings are similar to those seen with reversible
posterior leukoencephalopathy syndrome (RPLS; also called posterior reversible encephalopathy syndrome [PRES]) [23,24]. (See "Reversible posterior
leukoencephalopathy syndrome", section on 'Neuroimaging'.)

A prospective study reported that transcranial Doppler examinations after delivery showed depressed dynamic cerebral autoregulation and increased
cerebral perfusion pressure in patients with eclampsia compared with other groups [25]. Cerebral perfusion pressure was similar for those with
eclampsia and those with preeclampsia with severe features.

Electroencephalography — Information on electroencephalography (EEG) in eclampsia is limited. A literature review reported postictal EEG
abnormalities were common in patients with eclampsia, and the EEG became normal with prolonged postpartum follow-up [26]. The studies were of low
methodologic quality and all but one were published between 1955 and 1984; findings using contemporary equipment and practices have not been
published. (See "Electroencephalography (EEG) in the diagnosis of seizures and epilepsy".)

Neurohistopathology — A classic report from 1973 described neurohistopathology in patients with eclampsia who underwent autopsy shortly after
death [27]. In this series, >50 percent of those who died within two days of seizing had cerebral hemorrhages. Petechial cortical hemorrhages were most
common, especially involving the occipital lobe. Diffuse cerebral edema and gross hemorrhage occurred less frequently. Cerebral venous thrombosis
was common in patients 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) [28]. 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.

DIAGNOSIS

In most patients, eclampsia is a clinical diagnosis based upon the occurrence of new-onset tonic-clonic seizures in the absence of other causative
conditions (eg, epilepsy, cerebral arterial ischemia and infarction, intracranial hemorrhage, drug use), typically in a patient with a hypertensive disorder
of pregnancy (preeclampsia, HELLP syndrome, gestational hypertension) ( table 4) [29]. Less commonly, focal or multifocal seizures or coma occurs
rather than a tonic-clonic seizure.
Even if criteria for a hypertensive disorder of pregnancy are not met, the diagnosis can be made in a pregnant person with seizures who has the typical
clinical and neuroimaging findings of reversible posterior leukoencephalopathy syndrome (RPLS; headache, confusion, visual symptoms, vasogenic
edema predominantly localized to the posterior cerebral hemispheres) [30,31]. (See "Reversible posterior leukoencephalopathy syndrome".)

Differential diagnosis — The differential diagnosis of new-onset seizures in a pregnant patient 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). There are many causes of
postpartum seizures ( table 5). 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, with or without coexistent eclampsia. Causes of sudden development of
neurologic symptoms include stroke, intracranial hemorrhage, brain mass lesion, toxic and metabolic encephalopathies, reversible cerebral
vasoconstriction syndrome, 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, kidney 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 in 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 HUS. TTP and HUS may be indistinguishable
from eclampsia that occurs in a patient with HELLP syndrome ( table 6) and approximately 10 to 20 percent of patients 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 (hemolysis, elevated liver enzymes, and low platelets)", section on
'Differential diagnosis' and "Diagnostic approach to suspected TTP, HUS, or other thrombotic microangiopathy (TMA)".)

POSTICTAL EVALUATION

Patients with preeclampsia who develop a generalized tonic-clonic seizure without persistent neurologic deficit require no diagnostic evaluation beyond
that for preeclampsia [33]. (See "Preeclampsia: Clinical features and diagnosis".)

Atypical cases should be evaluated for other causes of seizures, preferably by a neurologist. These patients include pregnant individuals who do not
meet criteria for diagnosis of preeclampsia ( table 7), HELLP syndrome, or gestational hypertension or who have persistent neurologic deficits,
prolonged loss of consciousness, onset of seizures >48 hours after giving birth, onset of seizures before 20 weeks of gestation, or seizures despite
adequate magnesium sulfate therapy. A neuroimaging study should be performed in these patients to evaluate for a culprit structural brain
abnormality.

MANAGEMENT

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

● Prevention of maternal hypoxia and trauma

● Treatment of severe hypertension, if present
● Terminating the seizure, if necessary
● Prevention of recurrent seizures
● Evaluation for delivery

Persistent seizures (status epilepticus), focal neurological signs, or seizure recurrence (particularly when magnesium levels are "therapeutic") should
raise concerns about an intracranial lesion/stroke. A neurology consultation and head imaging are generally indicated in this setting, in addition to
antiseizure therapy. (See "Convulsive status epilepticus in adults: Management" and "Evaluation and management of the first seizure in adults".)

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 [16]. Raised, padded bedrails provide
protection from trauma.

Treatment of hypertension — Antihypertensive therapy ( table 8) is administered to prevent stroke, which accounts for 15 to 20 percent of deaths in
patients with eclampsia. A common threshold for initiating antihypertensive therapy is a diastolic pressure ≥110 mmHg or systolic blood pressure ≥160
mmHg on repeated measurements, 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 [34]. The cerebral vasculature of patients 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 "Treatment of hypertension in pregnant and postpartum patients", section on 'Acute therapy of severe hypertension'.)

Antiseizure medication

Persistent seizure activity — The tonic-clonic phase of an eclamptic seizure usually resolves within two to three minutes ( table 3), at which time
magnesium sulfate can be initiated for prevention of recurrent seizures (see 'Magnesium sulfate prophylaxis' below). However, if the patient is actively
seizing for >5 minutes, we consider initiating treatment to terminate the seizure:

● Lorazepam 4 mg IV at a maximum rate of 2 mg/minute; may repeat at three to five minutes if the seizure continues.

● If IV access has not been established, midazolam 10 mg intramuscularly is usually effective. Two IV lines should be placed as soon as possible.

This approach is similar to the treatment of status epilepticus in nonpregnant adults with new-onset seizures, except valproate is avoided in pregnancy
[35,36]. Treatment is reviewed in detail separately. (See "Convulsive status epilepticus in adults: Classification, clinical features, and diagnosis", section
on 'Treatment'.)

Complications of prolonged maternal seizure activity may include hypoventilation and hypoxia, fever, and aspiration pneumonitis. Physiologically,
deleterious neurologic effects of status epilepticus worsen after approximately 30 minutes. (See "Convulsive status epilepticus in adults: Classification,
clinical features, and diagnosis", section on 'Complications and outcome'.)

Prevention of recurrent seizures

Magnesium sulfate prophylaxis — Magnesium sulfate is the antiseizure medication of choice in the setting of preeclampsia/eclampsia.
Treatment is primarily directed at prevention of recurrent seizures (prophylaxis) 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 patients with eclampsia will have repeated seizures if managed expectantly [37]. There is universal agreement that patients
with eclampsia require antiseizure medication 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.

● Evidence of magnesium sulfate's efficacy — Magnesium sulfate is the antiseizure medication 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 meperidine) for prevention of recurrent seizures in eclampsia [38-40]. Other 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 before 32 to 34 weeks
of gestation. (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 [41].
In two international multicenter trial arms, 905 patients with eclampsia were randomly assigned to receive either magnesium sulfate or diazepam
and another 775 patients 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:

• Patients allocated to magnesium sulfate therapy had one-half the rate of recurrent seizures of those allocated to diazepam (13 and 28 percent,
respectively).

• Patients 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 or perinatal mortality and/or morbidity between the two groups. (See "Preeclampsia:
Intrapartum and postpartum management and long-term prognosis", section on 'Drug of choice: Magnesium sulfate'.)

Dosing and toxicity — Our approach is described below and shown in the algorithm ( algorithm 1). The superiority of any one specific
magnesium regimen over another has not been established [42].

● 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 [9,43]. Using a loading dose at the lower end of this range (4 to 5 g) may be
prolong the duration of time to achieve peak levels, especially in patients with obesity [44,45].

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. Mixing the medication with 1 mL of lidocaine 2% solution reduces pain.
 These loading doses may be given safely to patients with impaired kidney function. (See "Preeclampsia: Intrapartum and postpartum management
and long-term prognosis", section on 'Dosing'.)

● Maintenance dose – We administer a maintenance dose of magnesium sulfate 2 g/hour as a continuous IV infusion to patients with good kidney
function. Maintenance doses of 1 to 2 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 resource-limited areas [46-48].

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 patients with good kidney function if the patient's clinical status is closely monitored and shows no evidence of potential
magnesium toxicity. (See "Preeclampsia: Intrapartum and postpartum management and long-term prognosis", section on 'Clinical assessment and
adjusting maintenance therapy'.)

In patients with impaired kidney function, maintenance dosing should be lower and dosed in consultation with a nephrologist or pharmacist and
magnesium levels should be monitored. The author of this topic 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. (See "Preeclampsia: Intrapartum and postpartum management and long-term prognosis", section on 'Dosing'.)

● Therapeutic magnesium level – 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 [49]. The dose should be adjusted according to the clinical response of individual patients.

● Toxicity, complications, and side effects – 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 patients with myasthenia gravis since it can precipitate a severe
myasthenic crisis.

Additional information on complications and side effects of magnesium sulfate therapy can be found separately. (See "Preeclampsia: Intrapartum
and postpartum management and long-term prognosis", section on 'Maternal side effects' and "Preeclampsia: Intrapartum and postpartum
management and long-term prognosis", section on 'Contraindications' and "Preeclampsia: Intrapartum and postpartum management and long-
term prognosis", section on 'Fetal and neonatal effects from magnesium sulfate' and "Preeclampsia: Intrapartum and postpartum management
and long-term prognosis", section on 'Drug interactions'.)

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

There is no role for mannitol in the routine care of patients with eclampsia [50]. It can be harmful because it can enter the brain and reverse the osmotic
gradient, thus increasing intracranial pressure. A neurologist should be consulted for management of patients 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 despite therapy — In patients with recurrent seizures on maintenance magnesium therapy, a magnesium level
should be obtained. These patients 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) [11,41,51]. If kidney function is normal,
magnesium sulfate maintenance doses of 2 to 3 g/hour are commonly used. The author of this topic administers a 4 g magnesium sulfate bolus and 3
g/hour maintenance infusion to patients with recurrent seizures and normal kidney function.

If more than two recurrences occur after these measures, we suggest discontinuing magnesium sulfate, administering fosphenytoin 20 mg PE/kg at 100
to 150 mg PE/min IV or phenytoin 20 mg/kg IV at a rate of up to 50 mg/minute (cardiac monitoring and frequent vital signs are required during these
infusions), and obtaining an urgent consultation from the neurology service. (Note: Fosphenytoin is prescribed as phenytoin sodium equivalents (mg PE)
and 1 mg PE is equivalent to 1 mg phenytoin sodium). (See "Convulsive status epilepticus in adults: Management".)

Fetal resuscitation — Fetal bradycardia lasting at several minutes is a common finding during and immediately after an eclamptic seizure and does not
necessitate emergency cesarean birth. In a series of 34 intrapartum eclamptic seizures, a prolonged fetal heart rate deceleration was documented in 79
percent of cases, and the mean duration of bradycardia was 5.8 minutes [52]. Fetal heart rate decelerations occurred a mean 2.7 minutes after the onset
of the seizure. Half of the fetuses with fetal heart rate changes subsequently developed fetal tachycardia and variability was minimal in 48 percent of
cases.

Stabilizing the mother by administering antiseizure medications 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 [16]. In the previously mentioned case series, 4 of 31 patients underwent emergency cesarean birth, two of whom had
suspected abruption, and there were no perinatal deaths [52]. (See "Acute placental abruption: Pathophysiology, clinical features, diagnosis, and
consequences" and "Acute placental abruption: Management and long-term prognosis".)

Delivery timing and route — Eclampsia is considered an absolute contraindication to continued expectant management. The definitive treatment for
eclampsia is prompt delivery; however, this does not necessarily preclude induction and a trial of labor [29,53]. 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 9). 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 patients in rural India at ≥34 weeks with eclampsia to
cesarean birth or induction after initial stabilization, planned cesarean did not significantly reduce the rate of adverse maternal or fetal outcomes, and
almost three-quarters of patients in the planned vaginal birth group succeeded in giving birth vaginally [54]. 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 patients and intrapartum care in higher resource settings.

By contrast, we would not induce patients 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 patients with severe preeclampsia/eclampsia remote from term successfully gave birth vaginally after induction of labor
[37,55,56]. Thus, cesarean birth is a reasonable option for these patients. 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 patients with preeclampsia. (See "Preeclampsia: Intrapartum and postpartum management and
long-term prognosis", section on 'Analgesia and anesthesia'.)

POSTPARTUM CARE

The postpartum care of patients 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 [57].

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 similarly maintain therapy for 24 to 48
hours. In either case, therapy may be continued in patients in whom signs and symptoms of preeclampsia have not started to improve and discontinued
in those who are clearly improving clinically (eg, diuresis of ≥100 mL/hour for two consecutive hours and the absence of symptoms). Decisions regarding
maternal activity, oral intake, and newborn 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 maternal stroke. Medications similar to those used
before delivery ( table 8) are often used postpartum, since most are compatible with breastfeeding. Target blood pressure is also the same. (See
"Treatment of hypertension in pregnant and postpartum patients", section on 'Acute therapy of severe hypertension' and "Treatment of hypertension in
pregnant and postpartum patients", section on 'Target blood pressure'.)

Patients with persistent hypertension may require transition to oral antihypertensive medications. If prepregnancy blood pressure was normal and the
patient is not hypertensive on oral medication, it is reasonable to stop the oral antihypertensive agent after three to four weeks and monitor blood
pressure to assess whether further treatment is indicated. (See "Treatment of hypertension in pregnant and postpartum patients", section on
'Postpartum hypertension'.)

Driving — Many health care professionals caring for patients with peripartum seizures have not considered issues relating to fitness to drive after an
eclamptic seizure [58]. 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 should have follow-up with a neurologist. These include patients who do not meet criteria for diagnosis of
preeclampsia ( table 7), gestational hypertension, or HELLP syndrome or who have persistent neurologic deficits, prolonged loss of consciousness,
onset of seizures >48 hours after giving birth, onset of seizures before 20 weeks of gestation, or seizures despite adequate magnesium sulfate therapy.

PREGNANCY OUTCOME

Maternal — Maternal complications occur in up to 70 percent of patients with eclampsia. The types and frequencies of complications from one review
are summarized in the table ( table 10). Additional complications include intracerebral hemorrhage, transient cortical blindness, and cardiorespiratory
arrest [37]. 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 patients with eclampsia [59,60].

Maternal mortality rates of 0 to 14 percent have been reported over the past few decades [1,6,8,61-63]. Maternal mortality and severe morbidity rates
are lowest among patients receiving regular prenatal care who are managed by experienced physicians in tertiary centers (maternal mortality 0 to 1.8
percent) [16,37,61,64-66]. The highest mortality rates are in low-resource countries where prenatal, intrapartum, and neonatal care are compromised by
limited resources [8,63,67]. 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 patients 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 — Preterm birth, placental abruption, 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 patients 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 newborns were small for gestational age.

LONG-TERM PROGNOSIS

Recurrence risk — Recurrent eclampsia occurs in 2 percent of subsequent pregnancies [68,69]. The risk of developing preeclampsia in subsequent
pregnancies can be reduced by the daily administration of low-dose aspirin, beginning at ≥12 weeks of gestation and ideally prior to 16 weeks (see
"Preeclampsia: Prevention"). If preeclampsia develops, the risk of eclampsia appears to be reduced by close maternal monitoring and timely
intervention [70].

The risk of recurrence was illustrated by a study that followed 159 nulliparous patients with a history of eclampsia and no preexisting hypertension
through 334 subsequent pregnancies in the era before low-dose aspirin prophylaxis [71]. 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 patients whose eclampsia occurred at ≤30 weeks of gestation in the index pregnancy. In these patients,
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, patients with a history of severe preeclampsia/eclampsia are at increased
risk of obstetric complications in subsequent pregnancies compared with patients with no such history. These problems include [68,69,71,72]:

● Placental abruption (2.5 to 6.5 versus 0.4 to 1.3 percent of the general obstetric population)
● Preterm birth (15 to 21 versus 12 percent)
● Fetal growth restriction (12 to 23 versus 10 percent)
● Perinatal mortality (4.6 to 16.5 versus 1 percent)

Patients 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 [71,72]. This risk appears to be the same whether they had eclampsia or another
manifestation of preeclampsia with severe features.

Long-term maternal health

● Future cardiovascular disease – Both preeclampsia and eclampsia are associated with an increased risk for development of cardiovascular and
cerebrovascular disease and diabetes later in life. These data are discussed elsewhere. (See "Preeclampsia: Intrapartum and postpartum
management and long-term prognosis", section on 'Prognosis'.)

Chronic hypertension develops in 0 to 78 percent (mean 24 percent) of patients with a history of preeclampsia/eclampsia [68,69,71-73]. 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 [69]). The risk appears to be highest in the subgroup of patients who
have subsequent pregnancies complicated by hypertension, parous patients with eclampsia, and patients with eclampsia remote from term
[68,69,71].

● Future seizure disorder – Patients with eclampsia may be at higher risk of a future seizure, but the absolute risk is small. In a retrospective study
that included 1615 patients with eclampsia, the adjusted hazard ratio for future seizures was 5.4 (95% CI 2.4-12.1), and the absolute risk was 1
seizure per 2200 person-years [74]. The authors did not distinguish patients who had one subsequent seizure from those who had recurrent
seizures.

● Other – In a study of 39 patients with a history of eclampsia, magnetic resonance imaging performed an average of 6.4 years following the index
pregnancy revealed that these patients had a higher prevalence of white matter lesions than matched controls with normotensive uncomplicated
pregnancies (odds ratio 3.3, 95% CI 1.05-10.60) [75]. Approximately 15 percent of patients in each group were currently hypertensive or on
antihypertensive therapy. The source and significance of these lesions are unclear; affected individuals do not appear to have increased functional
impairment as may be seen in other patients with white matter lesions. Another study of patients with eclampsia reported no objective cognitive
impairment as compared with controls when evaluated 2 to 20 years after delivery [76].

CAN ECLAMPSIA BE PREDICTED AND PREVENTED?

In patients who have been diagnosed with preeclampsia with severe features, prophylactic administration of magnesium sulfate can usually prevent
seizures (see "Preeclampsia: Intrapartum and postpartum management and long-term 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) [77].
The majority of patients with eclampsia have one or more antecedent symptoms in the hours prior to an eclamptic seizure, thus pregnant patients
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 [1,77-80]. In a systematic review, the most commonly reported symptoms (visual
disturbances, epigastric pain, and headache) neither accurately predicted, nor ruled out, imminent eclampsia [81].

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 [1,62,64]. While antihypertensive
treatment is recommended for patients with blood pressures ≥160/110 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 "Treatment of hypertension
in pregnant and postpartum patients".)

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

● Diagnosis – In most patients, eclampsia is a clinical diagnosis based upon the occurrence of new-onset tonic-clonic seizures in the absence of
other causative conditions (eg, epilepsy, cerebral arterial ischemia and infarction, intracranial hemorrhage, drug use) in a patient with a
hypertensive disorder of pregnancy (preeclampsia, gestational hypertension, HELLP syndrome [hemolysis, elevated liver enzymes, low platelets]
( table 4 and algorithm 2)). Some patients present with focal or multifocal seizures or coma. (See 'Diagnosis' above.)

● Differential diagnosis – Pregnancy is a precipitating factor for some disorders associated with seizure activity, such as thrombotic
thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS). TTP and HUS may be indistinguishable from eclampsia that occurs in a
patient with HELLP syndrome ( table 6) and approximately 10 to 20 percent of patients with preeclampsia/eclampsia have laboratory findings of
HELLP syndrome. (See 'Differential diagnosis' above.)

● Incidence – In patients not receiving antiseizure prophylaxis, an eclamptic seizure occurs in 2 to 3 percent of patients diagnosed with preeclampsia
with severe features and in 0 to 0.6 percent of those with preeclampsia without severe features. (See 'Epidemiology' above.)

● Clinical features

• Maternal signs/symptoms – Eclampsia is manifested by a generalized tonic-clonic seizure ( table 3). Most patients 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.)

• Fetal heart rate – Fetal bradycardia lasting at least three to five minutes is a common finding during and immediately after an eclamptic
seizure. Emergency cesarean birth 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.)

• Gestational age at occurrence – Eclampsia occurs before term in approximately 50 percent of patients. 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.)

● Prediction/prevention – The majority of patients with eclampsia have one or more antecedent symptoms in the hours prior to an eclamptic
seizure; however, the most commonly reported symptoms (visual disturbances, epigastric pain, and headache) neither accurately predicted, nor
ruled out, imminent eclampsia. Eclampsia may not be preventable with magnesium sulfate when onset is abrupt, early in pregnancy, or after
postpartum hospital discharge. (See 'Can eclampsia be predicted and prevented?' above.)

● Management – Our approach is described in the algorithm ( algorithm 1). Key management issues are: prevent maternal hypoxia and trauma,
treat severe hypertension (if present), treat prolonged seizure activity if present, prevent recurrent seizures with magnesium sulfate, and evaluate
for delivery. (See 'Key principles' above.)

• Termination of prolonged acute seizure activity – The tonic-clonic phase of an eclamptic seizure usually resolves within two to three minutes,
at which time magnesium sulfate can be initiated for prevention of recurrent seizures. If the patient is actively seizing for >5 minutes, we
consider administering:

- Lorazepam 4 mg IV at a maximum rate of 2 mg/minute; may repeat at three to five minutes if the seizure continues.

- If IV access has not been established, midazolam 10 mg intramuscularly is usually effective. Two IV lines should be placed as soon as
possible.

• Magnesium sulfate prophylaxis – For patients with eclampsia, we recommend prophylaxis 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 'Dosing
and toxicity' above.)

• Antihypertensive therapy – A common threshold for initiating antihypertensive therapy is sustained diastolic pressures greater than 110
mmHg or systolic blood pressures ≥160 mmHg. Drugs options are described in the table ( table 8). (See 'Treatment of hypertension' above.)

• Recurrent seizures – In patients with recurrent seizures on maintenance magnesium therapy, a magnesium level should be obtained. The
author administers a 4 g magnesium sulfate bolus and 3 g/hour maintenance infusion to patients with recurrent seizures and normal renal
function. (See 'Management of recurrent seizures despite therapy' above.)

• Neurology consultation – Persistent seizures (status epilepticus), recurrent seizures while on magnesium seizure prophylaxis, focal
neurological signs, or seizure occurrence when magnesium levels are “therapeutic” should raise concerns about an intracranial lesion/stroke. A
neurology consultation and head imaging are generally indicated in this setting, in addition to antiseizure therapy. (See 'Management of
recurrent seizures despite therapy' above.)

• Delivery – 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 timing and route' above.)

● Postpartum care and course – 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 similarly maintain therapy for 24 to 48 hours. (See 'Duration of magnesium sulfate therapy' above.)

● Pregnancy outcome – The types and frequencies of complications from one review are summarized in the table ( table 10). (See 'Pregnancy
outcome' above.)

● Long-term prognosis

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

• In addition to preeclampsia/eclampsia, patients 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.)

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Topic 1662 Version 66.0
GRAPHICS

In a patient with preeclampsia, the presence of one or more of the following indicates a diagnosis of "preeclampsia with
severe features"

Severe blood pressure elevation:

Systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110 mmHg on 2 occasions at least 4 hours apart while the patient is on bedrest; however,
antihypertensive therapy generally should be initiated upon confirmation of severe hypertension, in which case criteria for severe blood pressure elevation can be
satisfied without waiting until 4 hours have elapsed

Symptoms of central nervous system dysfunction:

New-onset cerebral or visual disturbance, such as:
Photopsia, scotomata, cortical blindness, retinal vasospasm
and/or
Severe headache (ie, incapacitating, "the worst headache I've ever had") or headache that persists and progresses despite analgesic therapy with acetaminophen
and not accounted for by alternative diagnoses

Hepatic abnormality:

Impaired liver function not accounted for by another diagnosis and characterized by serum transaminase concentration >2 times the upper limit of the normal range
and/or
Severe persistent right upper quadrant or epigastric pain unresponsive to medication and not accounted for by an alternative diagnosis

Thrombocytopenia:

Platelet count <100,000 platelets/microL

Kidney function impairment:

Serum creatinine >1.1 mg/dL [97.2 micromol/L]

and/or
Doubling of the serum creatinine concentration in the absence of other kidney disease

Pulmonary edema

Reference:
1. American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 222: Gestational Hypertension and Preeclampsia. Obstet Gynecol 2020; 135:e237.

Graphic 76975 Version 29.0

Clinical factors that have been associated with an increased risk of developing preeclampsia

Nulliparity

Preeclampsia in a previous pregnancy

Age >40 years or <18 years

Family history of preeclampsia

Chronic hypertension

Chronic kidney disease

Autoimmune disease (eg, antiphospholipid syndrome, systemic lupus erythematosus)

Vascular disease

Diabetes mellitus (pregestational and gestational)

Multifetal gestation

Obesity

Minority racial or ethnic group or otherwise disadvantaged

Hydrops fetalis

Poorly controlled hyperthyroidism

Patient themself was small for gestational age

Fetal growth restriction, abruption, or fetal demise in a previous pregnancy

Prolonged interpregnancy interval if the previous pregnancy was normotensive; if the previous pregnancy was preeclamptic, a short interpregnancy interval increases the
risk of recurrence

Male partner-related factors (new male partner, limited sperm exposure [eg, previous use of barrier contraception])

In vitro fertilization

Sleep disordered breathing

Elevated blood lead level

Posttraumatic stress disorder

By comparison, smoking decreases the risk of preeclampsia, and Asian females and Hispanic females have a lower risk of preeclampsia than White females and a
much lower risk than Black females.

Graphic 61266 Version 16.0

Phases of tonic-clonic seizures

Aura (None)

Tonic phase (10 to 20 seconds)

Sudden loss of consciousness

Loss of posture with high risk of self injury depending on activity

Brief flexion of arms, eyes deviated upward

Extension of back, neck, arms, and legs

Involuntary crying out from contraction of respiratory muscles

Shallow respiration, cyanosis may occur

Ends with tremors that gradually slow and merge with clonic phase

Clonic phase (30 to 90 seconds)

Brief, violent, generalized flexor contractions alternating with progressively longer muscle relaxation

Cyanosis

Possible cheek or tongue biting

Foamy salivation

Possible loss of bowel or bladder control

Ends with deep inspiration, sustained muscle relaxation

Postictal phase (Minutes to several hours)

Headache, mild confusion

Muscles sore

Fatigue, patient may sleep and awake refreshed

Other features

Fast heart rate

Elevated blood pressure

Respiratory and metabolic acidosis

Dilated pupils

Risk of vertebral fracture, pneumonia

Graphic 54942 Version 2.0

Definitions/diagnostic criteria for the hypertensive disorders in pregnancy

Gestational hypertension New onset of systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg on at least 2 occasions 4 hours apart
after 20 weeks of gestation in a previously normotensive individual
And:
No proteinuria
No signs/symptoms of preeclampsia-related end-organ dysfunction (eg, thrombocytopenia, renal insufficiency, elevated liver
transaminases, pulmonary edema, cerebral or visual symptoms)

Preeclampsia New onset of systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg on at least 2 occasions at least 4 hours
apart after 20 weeks of gestation in a previously normotensive individual. Patients with systolic blood pressure ≥160 mmHg and/or
diastolic blood pressure ≥110 mmHg should have blood pressure confirmed within a short interval (minutes) to facilitate timely
administration of antihypertensive therapy.
And:
Proteinuria (≥300 mg per 24-hour urine collection [or this amount extrapolated from a timed collection], or protein:creatinine ratio
≥0.3, or urine dipstick reading ≥2+ [if other quantitative methods are not available]).

In a patient with new-onset hypertension without proteinuria, the diagnosis of preeclampsia can still be made if any features of
severe disease are present.

Preeclampsia with severe In a patient with preeclampsia, presence of any of the following findings are features of severe disease:
features Systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110 mmHg on 2 occasions at least 4 hours apart (unless
antihypertensive therapy is initiated before this time)
Thrombocytopenia (platelet count <100,000/microL)
Impaired liver function as indicated by liver transaminase levels at least twice the normal concentration or severe persistent right
upper quadrant or epigastric pain unresponsive to medication and not accounted for by alternative diagnoses, or both
Progressive renal insufficiency (serum creatinine concentration >1.1 mg/dL [97 micromol/L] or doubling of the serum creatinine
concentration in the absence of other renal disease)
Pulmonary edema
Persistent cerebral or visual disturbances

Eclampsia A generalized seizure in a patient with preeclampsia that cannot be attributed to other causes

HELLP syndrome Hemolysis, Elevated Liver enzymes, and Low Platelets. Hypertension may be present (HELLP in such cases is often considered a
variant of preeclampsia).

Chronic (preexisting) Hypertension diagnosed or present before pregnancy or on at least two occasions before 20 weeks of gestation. Hypertension
hypertension that is first diagnosed during pregnancy and persists for at least 12 weeks postpartum is also considered chronic hypertension.

Blood pressure criteria during pregnancy are:

Systolic ≥140 mmHg and/or diastolic ≥90 mmHg
Prepregnancy and 12 weeks postpartum blood pressure criteria are:
Stage 1 – Systolic 130 to 139 mmHg or diastolic 80 to 89 mmHg
Stage 2 – Systolic ≥140 mmHg or diastolic ≥90 mmHg

Chronic hypertension with Any of these findings in a patient with chronic hypertension:
superimposed preeclampsia* A sudden increase in blood pressure that was previously well-controlled or an escalation of antihypertensive therapy to control
blood pressure
New onset of proteinuria or a sudden increase in proteinuria in a patient with known proteinuria before or early in pregnancy
Significant new end-organ dysfunction consistent with preeclampsia after 20 weeks of gestation or postpartum

Chronic hypertension with Any of these findings in a patient with chronic hypertension and superimposed preeclampsia:
superimposed preeclampsia Systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110 mmHg despite escalation of antihypertensive therapy
with severe features Thrombocytopenia (platelet count <100,000/microL)
Impaired liver function as indicated by liver transaminase levels at least twice the normal concentration or severe persistent right
upper quadrant or epigastric pain unresponsive to medication and not accounted for by alternative diagnoses, or both
New-onset or worsening renal insufficiency
Pulmonary edema
Persistent cerebral or visual disturbances

* Precise diagnosis is often challenging. High clinical suspicion is warranted given the increase in maternal and fetal-neonatal risks associated with superimposed
preeclampsia.

Adapted from:
1. Gestational hypertension and preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol 2020; 135:e237.
2. Report of the National High Blood Pressure Education Program Working Group on high blood pressure in pregnancy. Am J Obstet Gynecol 2000; 183:S1.

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Causes of postpartum seizures and/or coma

Obstetric

Eclampsia
Sheehan syndrome
Amniotic fluid embolism

Anesthetic

Dural puncture with leakage of cerebrospinal fluid

Air embolism

Neurologic

Primary seizure disorder

Intracranial structural lesion
Stroke
Intracranial hemorrhage
Posterior reversible encephalopathy syndrome
Reversible cerebral vasoconstrictor syndrome
Spontaneous leakage of cerebrospinal fluid

Metabolic

Withdrawal syndrome (alcohol or drug withdrawal)

Electrolyte abnormalities
Uremia
Hypoglycemia
Thyroid abnormalities
Hypocalcemia

Infectious

Meningitis or encephalitis
Sepsis

Autoimmune

Systemic lupus erythematosus

Sjögren's disease
Wegener's granulomatosis
Sarcoidosis

Psychiatric

Pseudoseizure

Other

Porphyria
Thrombotic thrombocytopenic purpura
Post-traumatic brain injury

Adapted from: Causer E, Birchall I, Simchovic G, Pascoal E. Postpartum seizure as a complication of dural puncture and intracranial hypotension. CMAJ 2023 July 10;195:E905-8. doi: 10.1503/cmaj.230063.

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Comparison of frequency of signs, symptoms, and laboratory findings in TTP, HUS, HELLP, and AFLP

TTP HUS HELLP AFLP

Abdominal pain ++ ++ ++ ++

Low ADAMST13 activity +/++ – –/+ ?

Anemia ++ ++ + +

Elevated lactic dehydrogenase ++ very high values ++ very high values ++ +/++

Elevated transaminases –/+ –/+ ++ ++

Fever + – – +

Headache or visual disturbance ++ – ++ –/+

Hypertension +/++ ++ ++ –

Jaundice – – + +

Nausea and vomiting ++ ++ ++ ++

Proteinuria + and hematuria ++ ++ –

Thrombocytopenia ++ ++ ++ +

von Willebrand factor ++ ++ – ?

Hypoglycemia – – –/+ ++

TTP: thrombotic thrombocytopenic purpura; HUS: hemolytic uremic syndrome; HELLP: hemolysis, elevated liver function tests, low platelets; AFLP: acute fatty liver of
pregnancy; +: prevalence of finding in affected patients.

Adapted from:
1. Stella CL, Dacus J, Guzman E, et al. The diagnostic dilemma of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in the obstetric triage and emergency department: lessons from 4
tertiary hospitals. Am J Obstet Gynecol 2009; 200:381. Original Table 4.
2. Pourrat O, Coudroy R, Pierre F. Differentiation between severe HELLP syndrome and thrombotic microangiopathy, thrombotic thrombocytopenic purpura and other imitators. Eur J Obstet Gynecol
Reprod Biol 2015;189:68. Table 1.

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Diagnostic criteria for preeclampsia

Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg on at least 2 occasions at least 4 hours apart after 20 weeks
of gestation in a previously normotensive patient AND the new onset of 1 or more of the following*:

Proteinuria ≥0.3 g in a 24-hour urine specimen or protein/creatinine ratio ≥0.3 (30 mg/mmol) in a random urine specimen or dipstick ≥2+ if a quantitative
measurement is unavailable

Platelet count <100,000/microL

Serum creatinine >1.1 mg/dL (97.2 micromol/L) or doubling of the creatinine concentration in the absence of other kidney disease

Liver transaminases at least twice the upper limit of the normal concentrations for the local laboratory

Pulmonary edema

New-onset and persistent headache not accounted for by alternative diagnoses and not responding to usual doses of analgesics ¶

Visual symptoms (eg, blurred vision, flashing lights or sparks, scotomata)

Preeclampsia is considered superimposed when it occurs in a patient with chronic hypertension. Superimposed preeclampsia is characterized by worsening or
resistant hypertension (especially acutely), the new onset of proteinuria or a sudden increase in proteinuria, and/or significant new end-organ dysfunction in a patient
with chronic hypertension. It typically occurs after 20 weeks of gestation or postpartum.

Definitions/diagnostic criteria for preeclampsia are generally similar worldwide except the International Society for the Study of Hypertension in Pregnancy definition
also includes signs of uteroplacental dysfunction (eg, fetal growth restriction, abnormal angiogenic markers, abnormal umbilical artery Doppler, abruption, fetal
demise).

* If systolic blood pressure is ≥160 mmHg and/or diastolic blood pressure is ≥110 mmHg, confirmation within minutes is sufficient.

¶ Response to analgesia does not exclude the possibility of preeclampsia.

Adapted from:
1. American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 222: Gestational Hypertension and Preeclampsia. Obstet Gynecol 2020; 135:e237.
2. Magee LA, Brown MA, Hall DR, et al. The 2021 International Society for the Study of Hypertension in Pregnancy classification, diagnosis & management recommendations for international practice.
Pregnancy Hypertens 2022; 27:148.

Graphic 79977 Version 39.0

Antihypertensive medications for urgent blood pressure control in pregnancy

Drug Initial dose Follow-up

Labetalol 20 mg IV gradually over 2 minutes. Repeat BP measurement at 10-minute intervals:

If BP remains above target level at 10 minutes, give 40 mg IV
over 2 minutes.
If BP remains above target level at 20 minutes, give 80 mg IV
over 2 minutes.
If BP remains above target level at 30 minutes, give 80 mg IV
over 2 minutes.
If BP remains above target level at 40 minutes, give 80 mg IV
over 2 minutes.

Cumulative maximum dose is 300 mg. If target BP is not achieved,

switch to another class of agent. Hold dose if heart rate <60 beats
per minute.

A continuous IV infusion of 1 to 2 mg/minute can be used instead Adjust dose within this range to achieve target blood pressure.
of intermittent therapy or started after 20 mg IV dose.
Cumulative maximum dose is 300 mg. If target BP is not achieved,
Requires use of programmable infusion pump and continuous switch to another class of agent.
noninvasive monitoring of blood pressure and heart rate
(reduce/discontinue infusion if heart rate <60 beats per minute).

Hydralazine 5 mg IV gradually over 1 to 2 minutes.* Repeat BP measurement at 20-minute intervals:

Adequate reduction of blood pressure is less predictable than with If BP remains above target level at 20 minutes, give 5 or 10
IV labetalol. mg IV over 2 minutes, depending on the initial response.
If BP remains above target level at 40 minutes, give 5 to 10
mg IV over 2 minutes, depending on the previous response.

Cumulative maximum dose is 20 to 30 mg per treatment event. If

target BP is not achieved, switch to another class of agent.

Nicardipine (parenteral) The initial dose is 5 mg/hour IV by continuous infusion titrated up Adjust dose within this range to achieve target BP.
to 15 mg/hour to achieve target BP 130 to 150/80 to 100 mmHg.
The effect of dose titrations may not be observed for 5 to 15
minutes; rapid titration should be avoided to minimize risk of
overshooting dose.

Requires use of a programmable infusion pump and continuous

noninvasive monitoring of blood pressure and heart rate.

Nifedipine immediate release* 10 mg orally. Repeat BP measurement at 20-minute intervals:

If BP remains above target at 20 minutes, give 10 or 20 mg
orally, depending on the initial response.
If BP remains above target at 40 minutes, give 10 or 20 mg
orally, depending on the previous response.

If target BP is not achieved, switch to another class of agent.

Nifedipine extended release 30 mg orally. If target BP is not achieved in 1 to 2 hours, another dose can be
administered.

If target BP is not achieved, switch to another class of agent.

IV: intravenous; BP: blood pressure; FHR: fetal heart rate.

* We caution against use of immediate-release oral nifedipine, although some obstetric guidelines have endorsed its use as a first-line option for emergency treatment
of acute, severe hypertension in pregnancy or postpartum (other options were labetalol and hydralazine), particularly when IV access is not in place. In most cases, use
of immediate-release oral nifedipine will be safe and well tolerated; however, there is a risk of an acute, precipitous fall in blood pressure, which may result in a
reduction in uteroplacental perfusion. The immediate-release preparations are also associated with a higher incidence of headache and tachycardia. In nonpregnant
adults, the package insert states that "nifedipine capsules should not be used for the acute reduction of blood pressure."

Adapted from:
1. American College of Obstetricians and Gynecologists. Gestational hyertension and preeclampsia. Practice Bulletin, Number 222. Obstet Gynecol 2020; 135:e237.
2. Bernstein PS, Martin JN Jr, Barton JR, et al. National Partnership for Maternal Safety: Consensus Bundle on Severe Hypertension During Pregnancy and the Postpartum Period. Obstet Gynecol 2017;
130:347.

Graphic 110261 Version 14.0

Approach to treatment of eclamptic seizures

Neurology consultation and neuroimaging are indicated to rule out an intracranial lesion/stroke if seizures are persistent, recurrent on "therapeutic" levels of
magnesium, and/or focal neurological signs are present.

IV: intravenous; PE: phenytoin sodium equivalents.

* Refer to UpToDate content on treatment of hypertension in pregnancy.

¶ Most initial eclamptic seizures are self-limiting (lasting 1 to 2 minutes). Supportive care is provided and medication is administered to prevent recurrence.

Δ Refer to UpToDate content on eclampsia for information on management of patients with impaired renal function.

◊ 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.

Graphic 139909 Version 5.0

Bishop scoring system [1]

0 1 2 3

Dilation, cm Closed 1 to 2 3 to 4 ≥5 to 6

Effacement, % 0 to 30 40 to 50 60 to 70 ≥80

Station* -3 -2 -1, 0 +1, +2

Cervical consistency Firm Medium Soft

Position of the cervix Posterior Midposition Anterior

* Based on a -3 to +3 scale.

Reference:

1. ​Bishop EH. Pelvic scoring for elective induction. Obstet Gynecol 1964; 24:266.

Graphic 65320 Version 11.0

Summary of maternal and neonatal outcomes in pregnancies complicated by eclampsia

Outcome Frequency (percent)

Abruption 7 to 10

Disseminated intravascular coagulation 7 to 11

Pulmonary edema 3 to 5

Acute renal failure 5 to 9

Aspiration pneumonia 2 to 3

Cardiopulmonary arrest 2 to 5

Liver hematoma 1

HELLP syndrome 10 to 15

Perinatal death 5.6 to 11.8

Preterm birth 50

Adapted from: Sibai BM. Obstet Gynecol 2005; 105:402.

Graphic 70241 Version 3.0

Stroke mortality related to blood pressure and age

Stroke mortality rate, pictured on a log scale with 95% CI, in each decade of age in relation to the estimated usual systolic and diastolic blood pressure at the start of
that decade. Stroke mortality increases with both higher pressures and older ages. For diastolic pressure, each age-specific regression line ignores the left-hand point
(ie, at slightly less than 75 mmHg) for which the risk lies significantly above the fitted regression line (as indicated by the broken line below 75 mmHg).

CI: confidence interval.

Data from Prospective Studies Collaboration, Lancet 2002; 360:1903.

Graphic 66793 Version 5.0

Diagnostic evaluation of a pregnant or postpartum woman with persistent systolic blood pressure ≥140 mmHg or diastolic
blood pressure ≥90 mmHg*

A reduction in blood pressure early in pregnancy is a normal physiologic occurrence. For this reason, women with chronic hypertension may be normotensive at their
first few prenatal visits. Later in pregnancy, when their blood pressure returns to its prepregnancy baseline, they may appear to be developing preeclampsia or
gestational hypertension if there are no documented prepregnancy blood pressure measurements.

BP: blood pressure.

* Blood pressure should be elevated on at least two occasions at least four hours apart. However, if systolic pressure is ≥160 mmHg or diastolic pressure is ≥110
mmHg, confirmation after a short interval, even within a few minutes, is acceptable to facilitate timely initiation of antihypertensive therapy.

¶ The onset of preeclampsia and gestational hypertension is almost always after 20 weeks of gestation. Preeclampsia before 20 weeks of gestation may be associated
with a complete or partial molar pregnancy or fetal hydrops. Postpartum preeclampsia usually presents within two days of delivery. The term "delayed postpartum
preeclampsia" is used for signs and symptoms of the disease leading to readmission more than two days but less than six weeks after delivery.

Δ Significant proteinuria is defined as ≥0.3 g in a 24-hour urine specimen or protein/creatinine ratio ≥0.3 (mg/mg) (34 mg/mmol) in a random urine specimen or
dipstick ≥1+ if a quantitative measurement is unavailable.

◊ Almost all women with the new onset of hypertension and proteinuria at this gestational age or postpartum have preeclampsia, but a rare patient may have occult
renal disease exacerbated by the physiologic changes of pregnancy. An active urine sediment (red and white cells and/or cellular casts) is consistent with a proliferative
glomerular disorder but not a feature of preeclampsia. Women with chronic hypertension who had proteinuria prior to or in early pregnancy may develop
superimposed preeclampsia. This can be difficult to diagnose definitively, but should be suspected when blood pressure increases significantly (especially acutely) in
the last half of pregnancy/postpartum or signs/symptoms associated with the severe end of the disease spectrum develop.

§ Photopsia (flashes of light), scotomata (dark areas or gaps in the visual field), blurred vision, or temporary blindness (rare); severe headache (ie, incapacitating, "the
worst headache I've ever had") or headache that persists and progresses despite analgesic therapy; altered mental status. Seizure occurrence upgrades the diagnosis
to eclampsia.

¥ The differential diagnosis of preeclampsia with severe features includes but is not limited to:
Antiphospholipid syndrome
Acute fatty liver of pregnancy
Thrombotic thrombocytopenic purpura (TTP)
Hemolytic uremic syndrome (HUS)

The laboratory findings in these disorders overlap with those in preeclampsia with severe features. (Refer to table in the UpToDate topic on the clinical manifestations
and diagnosis of preeclampsia.) The prepregnancy history, magnitude and spectrum of laboratory abnormalities, and additional presence of signs and symptoms not
typically associated with preeclampsia help in making the correct diagnosis, which is not always possible during pregnancy.

In addition, a variety of medical disorders may be associated with hypertension and one or more of the signs and symptoms that occur in women with preeclampsia
with severe features. These patients can usually be distinguished from patients with preeclampsia by taking a detailed history, performing a thorough physical
examination, and obtaining relevant laboratory studies.

‡ In contrast to preeclampsia, gestational hypertension is not associated with end-organ involvement, so neither proteinuria nor the symptoms or laboratory findings
of preeclampsia are present. Refer to UpToDate topic on gestational hypertension.
Graphic 119141 Version 3.0
Contributor Disclosures
Errol R Norwitz, MD, PhD, MBA Patent Holder: Bayer [Prediction test for preeclampsia]. Consultant/Advisory Boards: Bio-Rad [Technical advances for the diagnosis,
monitoring, and treatment of reproductive disorders]; Cognitive Care/Early Detect [AI platform for early risk detection and quantification]. Other Financial Interest:
NICHD [Board of Scientific Counselors]. All of the relevant financial relationships listed have been mitigated. Charles J Lockwood, MD, MHCM No relevant financial
relationship(s) with ineligible companies to disclose. Steven C Schachter, MD Patent Holder: Supernus Pharmaceuticals [Epilepsy]. All of the relevant financial
relationships listed have been mitigated. Vanessa A Barss, MD, FACOG No relevant financial relationship(s) with ineligible companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and
through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate
standards of evidence.

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