Preeclampsia and Eclampsia Revisited

Sherri A. Longo, MD; Chi P. Dola, MD; Gabriella Pridjian, MD


South Med J. 2003;96(9) 

In This Article


Preeclampsia affects only pregnant women and is diagnosed when hypertension and proteinuria occur after 20 weeks' gestation. Edema is often seen but is not required to make the diagnosis. If seizures occur as a complication of preeclampsia, the term eclampsia is used. During the past several years, preeclampsia-eclampsia has been the second- or third-leading cause of maternal death[32] and is a common cause of fetal morbidity and wastage.

Preeclampsia affects approximately 4.5 to 11.2% of pregnancies in industrialized countries[33] and occurs more commonly in patients at the extremes of the reproductive age range. It is seen more often in primigravid women than in multiparous women. Recent epidemiologic studies suggest that multiparous women with different partners have a higher risk for preeclampsia than do multiparous women with the same partner,[34,35] perhaps because of a protective effect of repeated exposure to specific antigens.

The cause of preeclampsia remains unknown. Because preeclampsia is a compilation of specific signs and symptoms with different causes, it has been suggested that it is a syndrome rather than a disease.[36] Preeclampsia is more likely to occur in women with multiple gestations, underlying hypertension, and chronic illnesses such as autoimmune disease, diabetes mellitus, and renal disease. Recently, an association of preeclampsia with thrombophilia has been identified, particularly factor V Leiden heterozygote deficiency,[37,38] activated protein C resistance,[39] homocysteinemia,[40] and antiphospholipid syndrome.[41,42] Women who are carriers of certain inherited metabolic disorders seem to be at risk for preeclampsia and other complications of pregnancy. Specifically, women who are heterozygote carriers for β-oxidation disorders, particularly long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency,[43] are at risk for preeclampsia and acute fatty liver of pregnancy.

Although the specific cause of preeclampsia remains unknown, several factors contribute to the development of the disease spectrum, including the onset of vasospasm, activation of the coagulation system, oxidative stressors, increased inflammatory response, and ischemia.[44,45] The placenta is considered to be the inciting organ of preeclampsia-eclampsia. A rat model of preeclampsia has recently been developed, which should assist in unraveling these issues.[46] Current theory suggests that incomplete trophoblastic invasion of the uterine vascular endothelium results in thick-walled, muscular vessels rather than saclike, flaccid vessels, which is the normal response to trophoblastic invasion. The abnormally thick-walled vessels have higher resistance and less capacitance and cause a decrease in placental perfusion, leading to hypoxia.[47] Hypoxia in turn directly or indirectly causes several pathophysiologic abnormalities, particularly endothelial damage.

Changes in virtually all organ systems occur in preeclampsia-eclampsia. Intense vasospasm occurs probably in response to the higher sensitivity to all endogenous pressors, particularly angiotensin II.[21] The hypervolemia seen in normal pregnancy does not occur.[48] Decreased intravascular volume and hemoconcentration occur at least in part because of endothelial cell damage that promotes leakage of fluid and protein from the intravascular to the interstitial space. The leakage causes contraction of the intravascular space and expansion of the interstitial space (ie, edema).

Edema of the liver and hepatocellular necrosis results in leakage of aminotransferases and lactate dehydrogenase into the maternal circulation. Bilirubin is rarely increased in preeclampsia.[49] Hepatic hemorrhage, although rare, may manifest as a subcapsular hematoma. Rupture of a hepatic subcapsular hematoma is a life-threatening complication and a surgical emergency.

Women with preeclampsia have a decrease in glomerular filtration and renal blood flow. This is thought to be a result of vasospasm and glomerular capillary endothelial edema (ie, glomerular endotheliosis) that renders many glomeruli nonfunctional. Glomerular endotheliosis has been described as the classic pathologic renal lesion of preeclamptic women.[50] An increase in the blood uric acid level due to decreased renal perfusion or to increased production by poorly perfused tissue[51] has long been recognized as a consistent feature of preeclampsia.[52] Proteinuria, primarily due to increased glomerular permeability and damage,[53] is an integral part of the diagnosis of preeclampsia. Oliguria, defined as <500 ml/24 h, may occur secondary to hemoconcentration and decreased renal perfusion. Persistent oliguria may indicate acute tubular necrosis, the most common type of acute renal failure seen in preeclampsia.[54]

Cerebral edema, cerebral hemorrhage, temporary blindness, and seizures are some of the neurologic complications associated with preeclampsia and eclampsia. Other central nervous system manifestations include persistent headache, blurred vision, scotomata, and hyperreflexia.

Thrombocytopenia is the most common hematologic abnormality of severe preeclampsia. Microangiopathic hemolytic anemia may also occur. Changes in the coagulation cascade and in the fibrinolytic system may result in the syndrome of disseminated intravascular coagulopathy. The cause of these changes remains uncertain, but a hypothesis involves vascular endothelial damage that causes activation of platelets and the coagulation cascade.[55]

Maternal morbidity associated with preeclampsia is related to the multiorgan involvement of the disease. Maternal death is largely a result of complications from abruptio placentae, hepatic rupture, and eclampsia. Maternal mortality rates associated with preeclampsia range from 0 to 14%.[56,57]

Fetal morbidity and mortality in preeclamptic women can be substantial. Preeclamptic hypertension, similar to preexisting hypertension in pregnancy, is a risk factor for placental abruption and restriction of fetal growth. As one would expect, the rate of fetal complications parallels the severity of the disease.[58] Delivery of the fetus is more likely to be preterm if preeclampsia is severe and diagnosed early in the pregnancy. The sequelae of prematurity, particularly extreme prematurity (24-28 gestational weeks) may include respiratory distress syndrome, chronic lung disease, intraventricular hemorrhage, cerebral palsy, sepsis, necrotizing enterocolitis, and failure to thrive.

The diagnosis of preeclampsia has traditionally been made when a pregnant woman presents with the triad of hypertension, proteinuria, and edema after 20 weeks' gestation. In rare circumstances, however, preeclampsia has been diagnosed at less than 20 weeks' gestational age in a molar pregnancy. Current diagnostic criteria include only the presence of hypertension (in a woman with previously normal blood pressure) and proteinuria ( Table 1 ). Edema is no longer included as one of the diagnostic criteria, because of its wide spectrum of prevalence in normal pregnant women and because a small subset of women with preeclampsia-eclampsia have minimal edema. It is notable that women with occult or undiagnosed renal disease may present with apparently new-onset hypertension and proteinuria in pregnancy that may mimic preeclampsia. Obtaining a careful history, physical examination, and laboratory evaluation may clarify the diagnosis. In rare instances, a renal biopsy may be appropriate.[59]

Blood pressure values required for the diagnosis of preeclampsia include a systolic pressure in excess of 140 mm Hg and/or a diastolic pressure greater than 90 mm Hg (Korotkoff Phase V) recorded on two separate occasions at least 4 hours apart. Urinary protein excretion >300 mg/24 h is also required to make the diagnosis. The following laboratory studies should be performed to aid in evaluation of the severity of the disorder and guide management: a complete blood count with platelet count, liver enzymes, blood urea nitrogen, serum creatinine, and uric acid, as well as a 24-hour urine collection for protein excretion and creatinine clearance. Liver studies should include at least the transaminases (alanine aminotransferase and aspartate aminotransferase), lactate dehydrogenase, bilirubin, and albumin ( Table 2 ). Of note, in normal pregnancy, an increase in alkaline phosphatase is seen as a result of the presence of the placental isoform, and plasma albumin seems to decrease because of hemodilution. If the preeclamptic woman has bleeding, abruptio placentae, or microangiopathic hemolytic anemia, then her fibrinogen levels, prothrombin time, activated partial thromboplastin time, and fibrin degradation products also should be obtained.[60]

Preeclampsia has been classified as mild and severe. Severe preeclampsia consists of systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 110 mm Hg as well as significant proteinuria (>5.0 g/d), with or without evidence of effects on other organ systems. The following signs and symptoms, although variable in presence, are associated with severe preeclampsia: headache, visual disturbances, confusion, right upper quadrant or epigastric pain, impaired liver function, proteinuria, oliguria, pulmonary edema, microangiopathic hemolytic anemia, thrombocytopenia, and fetal intrauterine growth restriction. Preeclampsia is considered mild if hypertension and proteinuria as previously defined are present but not in the severe range and there is no evidence of other organ dysfunction.

Eclampsia is the occurrence of seizure activity not secondary to other convulsive disorders in women with signs and symptoms of preeclampsia. Convulsions may occur antepartum, intrapartum, or postpartum. The mechanisms leading to the development of convulsions in women with eclampsia may include cerebral edema, ischemia, hemorrhage, or transient vasospasm. Although eclampsia most often occurs in the setting of severe preeclampsia, it can occur in women with mild preeclampsia. There are no recognized clinical determinants of remote prediction of which women with preeclampsia will experience seizures. Severe headache and hyperreflexia, however, are common clinical precursors of eclamptic seizures.[61]

The combination of hemolysis, elevated liver function, and low platelets (HELLP) is a syndrome that is a variant of severe preeclampsia.[62] The complete spectrum of HELLP syndrome is seen in approximately 15% of women with preeclampsia-eclampsia.[63] It is generally agreed that pregnancies complicated by preeclampsia and HELLP syndrome are at even higher risk for maternal and/or fetal complications.[64]

The treatment and management of preeclampsia-eclampsia varies according to severity and gestational age at diagnosis. The definitive cure for preeclampsia is delivery of the fetus. Although optimal for the mother, however, preterm delivery may not be ideal for the fetus. Women suspected of having preeclampsia should be evaluated promptly and hospitalized at the time of diagnosis. Laboratory studies ( Table 2 ) should be obtained to determine the severity of the disease.

Delivery is indicated when preeclampsia is diagnosed at or beyond 38 weeks of pregnancy, regardless of the severity of the disease. However, individualized management of patients with mild preeclampsia at term when the cervix is not favorable for inducing labor is an alternative option that requires close observation and delivery at no later than 40 weeks' gestation ( Table 3 ).

When mild preeclampsia is diagnosed in a preterm pregnancy, hospital bed rest until delivery with close maternal and fetal surveillance (ie, expectant management) is recommended. In these premature gestations, consideration may be given to antenatal glucocorticoid therapy to accelerate fetal lung maturation ( Table 3 ). During the course of hospitalization, the woman with mild preeclampsia is monitored closely for signs and symptoms of severe preeclampsia or impending eclampsia (eg, persistent headache, hyperreflexia). Blood pressure measurements are usually recorded every 4 hours, and maternal weight should be assessed daily to detect excessive weight gain due to edema. Laboratory tests ( Table 2 ) should be obtained twice weekly or more frequently if signs or symptoms suggest progression of disease. Fetal surveillance is instituted in the form of daily fetal movement count, nonstress tests, and serial ultrasonographic evaluation of fetal growth and amniotic fluid volume to confirm fetal well-being. The optimal frequency of these tests has not been established but should depend on gestational age and the condition of the patient and fetus. More frequent antenatal fetal surveillance is required if the disease process worsens or if there is evidence of poor fetal growth or decreasing amniotic fluid volume. Expectant management usually continues until the pregnancy reaches term, the fetal lung maturity is documented by amniotic fluid studies, or severe preeclampsia or other complications develop.

Delivery is generally recommended for women with severe preeclampsia, even if the fetus is at less than 38 weeks' gestation ( Table 3 ). When severe preeclampsia is diagnosed in a pregnant woman at preterm gestation (usually <32 wk), however, an initial observation period and conservative expectant management in a tertiary care center may be attempted cautiously ( Table 3 ).[65,66] When eclampsia develops, expedient delivery is mandated, regardless of gestational age.

Once it is determined that delivery is required, labor induction should be performed without delay. The goals during the intrapartum period are to prevent seizures, stabilize blood pressure, and promote delivery. During labor and delivery, women with preeclampsia-eclampsia receive IV magnesium sulfate for seizure prophylaxis, usually as a loading dose of 4 to 6 g magnesium sulfate × 7H2O infused for 20 minutes followed by a continuous IV infusion at 2 g/h. Because magnesium is excreted in the urine, blood levels also depend on urine output. Serum blood levels should be monitored. The therapeutic range for magnesium sulfate is generally considered to be 4 to 8 mg/dl. In a patient with elevated creatinine or oliguria, the patient's magnesium level should be followed carefully and the magnesium sulfate infusion adjusted accordingly.

During labor, maternal blood pressure should be evaluated carefully and antihypertensive treatment should be initiated if systolic levels are persistently greater than 160 mm Hg or diastolic levels are consistently greater than 105 mm Hg. The most widely used antihypertensive medication in the intrapartum period for women with preeclampsia-eclampsia is hydralazine. It is best administered by IV bolus every 20 minutes. A starting dose of 5 mg is administered, which may be increased to 10 mg if indicated after 20 minutes of observation. The total dose of IV hydralazine in an acute therapeutic incident should not exceed 20 to 30 mg. An alternative antihypertensive medication used in this clinical setting is labetalol, which is usually administered as an IV bolus injection every 10 minutes at a starting dose of 20 mg, with subsequent dose doubled from the previous dose and the maximum acute total dose not to exceed 220 mg. Care should be taken not to decrease the patient's blood pressure acutely or to diastolic levels less than 80 mm Hg, because suboptimal uterine and placental perfusion may result in abnormal fetal heart rate patterns, such as fetal bradycardia or late deceleration.[67]

Continuous electronic fetal heart rate and uterine activity monitoring should be instituted in all cases. Vaginal delivery is safer than cesarean section in women with preeclampsia-eclampsia and usually should be attempted unless there are other obstetric indications for cesarean delivery. Certain women at preterm gestation with severe preeclampsia or eclampsia in whom the cervix is unfavorable for vaginal delivery may benefit from cesarean section without attempting labor induction.

Regional anesthesia is commonly used in women with preeclampsia. The sympathetic blockade and peripheral vascular dilation caused by local anesthetics used in epidural anesthesia may cause hypotension, however, unless meticulous attention is paid to anesthetic technique and proper gradual volume expansion.[68] When general anesthesia is required, it is crucial to carefully control maternal blood pressure during both the induction of and the recovery from anesthesia.

After delivery, the patient with preeclampsia-eclampsia is kept under close observation, and the magnesium sulfate infusion is continued for seizure prophylaxis. Resolution of the disease process, which manifests most commonly by diuresis, usually begins to occur within 24 hours. Some patients, however, especially those with HELLP syndrome or severe disease in midtrimester, may require intensive monitoring for several days before resolution occurs. Such patients may require magnesium sulfate treatment for more than 24 hours until diuresis occurs.


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