eMedicine Specialties > Emergency Medicine > Obstetrics & Gynecology

Pregnancy, Eclampsia

Author: Allysia M Guy, MD, Staff Physician, Department of Emergency Medicine, State University of New York Downstate Medical Center, Brooklyn, New York
Coauthor(s): Mark A Silverberg, MD, FACEP, MMB, Assistant Professor, Assistant Residency Director, Department of Emergency Medicine, State University of New York Downstate College of Medicine; Consulting Staff, Department of Emergency Medicine, Staten Island University Hospital, Kings County Hospital, University Hospital, State University of New York Downstate at Brooklyn
Contributor Information and Disclosures

Updated: Aug 11, 2009

Introduction

Background

Ten percent of all pregnancies are complicated by hypertension (HTN). Eclampsia and preeclampsia account for about half of these cases worldwide and have been recognized and described for years despite the general lack of understanding of the disease.¹ In the fifth century, Hippocrates noted that headaches, convulsions, and drowsiness were ominous signs associated with pregnancy. In 1619, Varandaeus coined the term eclampsia in a treatise on gynecology.²

Eclampsia is defined as the clinical presentation of an unexplained seizure, convulsion, or altered mental status in the setting of the signs and symptoms of preeclampsia. It is considered a complication of severe preeclampsia.² It typically occurs during or after the 20th week of gestation or in the postpartum period. 

The clinical manifestations of maternal preeclampsia are hypertension and proteinuria with or without coexisting systemic abnormalities involving kidney, liver, or blood. There is also a fetal manifestation of preeclampsia involving fetal growth restriction, reduced amniotic fluid, and abnormal fetal oxygenation.¹ HELLP syndrome is a severe form of preeclampsia and involves hemolytic anemia, elevated LFTs, and low platelet count.

Pathophysiology

Eclampsia is the progression from severe preeclampsia to seizures and coma and is thought to be due to hypertensive encephalopathy, vasogenic edema associated cortical ischemia, edema, or hemorrhage. The cause of preeclampsia and later eclampsia remains unclear. The main etiologic theories include abnormal trophoblastic invasion, coagulation abnormalities, vascular endothelial damage, cardiovascular maladaptation, immunologic phenomena, genetic predisposition, and dietary deficiencies or excess.²
 
It is believed that there is abnormal cerebral blood flow in the setting of extreme hypertension. Compensatory cerebral perfusion mechanisms are interrupted. Vessels become dilated with increased permeability and cerebral edema occurs and results in ischemia and encephalopathy. In extreme hypertension, the normal compensatory vasoconstriction may become defective. Several autopsy findings support this model and consistently reveal swelling and fibrinoid necrosis of vessel walls.²

Many uterovascular changes occur when a woman is pregnant. It is believed that these changes are due to the interaction between fetal and maternal allografts and result in systemic and local vascular changes. These system changes contribute to the brain pathology in eclampsia by inhibiting the regulation of cerebral perfusion. It has been shown that, in patients with eclampsia, the development of uteroplacental arteries is hindered.²

Many factors may contribute to this phenomenon. Endothelial cell dysfunction occurs in the vessels of these hypertensive women. Factors associated with endothelial dysfunction such as cellular fibronectin, von Willebrand factor, cell adhesion molecules (ie, P-selectin, vascular endothelial adhesion molecule-1 [VCAM-1], and intercellular adhesion molecule-1 [ICAM-1]), and cytokines (ie, interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]) have been shown to be increased in the systemic circulation of women suffering from this disease.¹ It is believed that antiangiogenic factors such as placental protein fms-like tyrosine kinase 1 (sFlt-1) and activin A antagonizes VEGF.³ Elevated levels of these proteins cause a reduction of VEGF and induce systemic and local endothelial cell dysfunction.¹

Reactive oxygen species have been shown to be pertinent for many cellular processes including angiogenesis, growth, and differentiation. Oxidative stress has been shown to stimulate activin A production and secretion from the placental and endothelial cells. Elevated levels of activin A are significantly associated with excessive oxidative stress.³ Additionally, oxidative stress has also been linked to endothelial dysfunction in preeclamptic patients. Studies in pregnant mouse models have proposed that there is a dysregulation in the ROS signaling pathway.^4,5 Leakage of proteins from circulation and generalized edema are sequelae of the endothelial dysfunction and thus a defining factor associated with preeclampsia and eclampsia. 

Studies also suggest that the oxidative stress, inflammation, and endothelial cell dysfunction is further mediated by increased systemic leukocyte activity. Histochemistry studies indicate that there is predominantly an increase in neutrophil infiltration of vasculature in patients with eclampsia.⁵

Evidence does exist demonstrating an increase in leptin molecules in the circulation, which induces oxidative stress on cells as well as induces platelet aggregation. This most likely contributes to the coagulopathy associated with the disease.^4,2  Additionally, imbalanced prostanoid productions as well as increased plasma antiphospholipids have also been implicated in the pathogenesis of eclampsia, though poorly understood.^6,2

Inflammation, neutrophil invasion, oxidative stress with endothelial injury, and angiogenesis impedance have all been implicated in the pathogenesis of preeclampsia; however, the pathophysiology as a whole remains to be elucidated. 

Frequency

United States

The reported incidence of eclampsia ranges from 1 in 2,000 to 1 in 3,448 pregnancies in the Western world. This rate is increased in lower socioeconomic populations, in woman younger than 20 years, in multifetal gestations, and in those without access to prenatal care.²

International

An estimated 10% of pregnancies are affected by hypertension worldwide.¹ Approximately one half of all hypertensive pregnancy disorders are due to preeclampsia.¹

Mortality/Morbidity

• The preeclampsia-eclampsia case-fatality rate is approximately 6.4 cases per 10,000 cases at delivery.¹
• The most significant maternal complications of eclampsia are related to permanent CNS damage secondary to recurrent seizures or intracranial bleeding. The maternal mortality rate is 8-36% in these cases.⁷
• The fetal mortality rate varies from 13-30% due to premature delivery and its complications. Placental infarcts, abruptio placentae, and intrauterine growth retardation also contribute to fetal demise.²
• Maternal death risk is approximately 1.8% in western countries. Higher mortality rates are associated with patients who have multiple seizures outside the hospital and those without prenatal care.
• In developing countries, mortality is as high as 14% and is associated with lack of resources and intensive care facilities required for supportive management.¹
• Mortality risks are increased for women aged 30 years and older, those without prenatal care, and black women.²
• Women who have eclampsia before 28 weeks' gestation have also been found to have a higher risk of death.²

Race

Black woman have an increased risk of mortality associated with preeclampsia, most likely due to inadequate access to prenatal care and increased incidences of genetic diseases associated with circulating antiphospholipids.² It has been proven that patients with elevated antiphospholipid plasma levels have a higher incidence of preeclampsia/eclampsia; however, whether this is due to the antiphospholipids themselves or some other underlying process is not clear.⁶

Age

Eclampsia usually occurs in patients at both extremes of reproductive age; however, the risk of eclampsia is greatest in women younger than 20 years. Mortality risk is higher for women older than 35 years who have suffered from eclampsia previously.²

Clinical

History

• Most eclamptic patients present with hypertension and seizures, with some combination of proteinuria and edema. However, hypertension, edema, and proteinuria may be absent in the setting of preeclampsia.⁷
• Hypertension has been absent 16% of the time, proteinuria absent 14%, and edema absent 26%.²
• Eclampsia can occur during the antepartum, intrapartum, and postpartum periods. Ninety percent of eclampsia cases occur after 28 weeks' gestation.²
• The natural progression of the disease is from symptomatic severe preeclampsia (differentiated from preeclampsia by specific vital signs, symptoms, and laboratory abnormalities) to seizures.
• Features of eclampsia include the following:
  • Seizure or postictal state (100%)
  • Headache (80%), usually frontal
  • Generalized edema (50%)
  • Vision disturbance (40%), such as blurred vision and photophobia
  • Right upper quadrant (RUQ) abdominal pain with nausea (20%)
  • Amnesia and other mental status changes

Physical

Findings at physical examination may include the following:

• Sustained systolic BP greater than 160 mm Hg or diastolic BP greater than 110 mm Hg
• Tachycardia
• Tachypnea
• Rales
• Mental status changes
• Hyperreflexia
• Clonus
• Papilledema
• Oliguria or anuria
• Localizing neurologic deficits
• Right upper quadrant (RUQ) or epigastric abdominal tenderness
• Generalized edema
• Small fundal height for the estimated gestational age
• Apprehension

Causes

The etiology of eclampsia is not fully understood:

• Studies in animal modes have suggested dysfunction of the uteroplacental bed related to altered endothelial, angiogenic factors, and vascular implantation.¹ This results in decreased uteroplacental perfusion pressure and ischemia with a subsequent release of cytokines and reactive oxygen species. The effect is a sympathetic and neurohormonal dysregulation of blood pressure, generalized vasoconstriction, and cellular and organ system dysfunction.³
• Other causes may include the following:
  • Altered cardiovascular reactivity
  • Increased capillary permeability
  • Widespread vasospasm
  • Microthrombi
  • Hypertension
  • Improper implantation of the placenta

Risk factors include the following:

• Nulliparity
• Family history of preeclampsia, prior preeclampsia and eclampsia²
• Poor outcome of previous pregnancy, including intrauterine growth retardation, abruptio placentae, or fetal death
• Preexisting medical condition - Obesity, chronic hypertension, renal disease, thrombophilias-antiphospholipid antibody syndrome, protein C deficiency and protein S deficiency, antithrombin deficiency, vascular and connective tissue disorders, gestational diabetes, and systemic lupus erythematosus²
• Multifetal gestations, hydatid mole, fetal hydrops, primigravida
• Teen pregnancy
• Primigravida
• Patient older than 35 years
• Lower socioeconomic status

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