Clinical:Preeclampsia

Other Names

First identified in pre-Roman times, preeclampsia is a multi-organ disorder affecting some 5 to 8 percent of pregnant women. Also known as toxemia, it usually occurs in the third trimester of pregnancy and is characterized by increased blood pressure, proteinuria and poor perfusion of many vital organs that can lead to a wide variety of other signs and symptoms. One of the challenges of research and clinical care has been the overlap with other conditions, such as gestational hypertension, chronic hypertension, and chronic hypertension with superimposed preeclampsia. The disorder can evolve to eclampsia, from the Greek word for lightening, characterized by seizures and/or coma.

Types

Preeclampsia can be mild or severe.

Mild preeclampsia is defined as: ^[1], ^[2].

• blood pressure of 140 mm Hg systolic or
• higher or 90 mm Hg diastolic or higher that occurs after 20 weeks of gestation in a woman with previously normal blood pressure
• proteinuria, defined as urinary excretion of 0.3 g protein or higher in a 24-hour urine specimen
• Severe preeclampsia is diagnosed if one or more of the following criteria is present:
  
• Blood pressure of 160 mm Hg systolic or higher or 110 mm Hg diastolic or higher on two occasions at least 6 hours apart while the patient is on bed rest;
• Proteinuria of 5 g or higher in a 24-hour urine specimen or 3+ or greater on two random urine samples collected at least 4 hours apart
• Oliguria of less than 500 mL in 24 hours
• Cerebral or visual disturbances
• Pulmonary edema or cyanosis
• Epigastric or right upper-quadrant pain
• Impaired liver function
• Thrombocytopenia
• Fetal growth restriction

Often thought of as a disease of the first pregnancy, it can occur in subsequent pregnancies. Fortunately, it is completely reversible with the delivery of the fetus.

Signs and Symptoms

Signs of preeclampsia usually come before the symptoms. The most common sequence is increased blood pressure followed by proteinuria.^[3]Most women with early preeclampsia are asymptomatic, hence the reason for frequent obstetric visits in late pregnancy. In most cases, signs such as increased blood pressure and proteinuria precede overt symptoms.

Preeclampsia is a disease of generalized poor perfusion, affecting many organs.

Headache is usually the first symptom, and is usually not relieved by standard measures such as acetaminophen.

Other symptoms including right upper quadrant or epigastric pain may indicate hepatic involvement, visual symptoms such as flashing lights (scotomata), or even blindness can indicate retinal arterial spasm and edema.

Late signs of severe disease can include congestive heart failure, fetal growth restriction, and placental abruption. Generalized edema particularly of the hands, feet and face can also be present.

Causes

The cause of preeclampsia is unknown. It is widely believed to be a reflection of endothelial damage and may relate to early events in placental implantation, but the precise cause remains unknown.

Diagnosis

The diagnosis is clinical, there is no gold-standard test. (see types above)

Treatment

The only definitive treatment of preeclampsia is delivery of the fetus. The exact timing on the decision to deliver depends on gestational age of the fetus and the severity of disease. Severe disease at term is always treated with delivery, whereas mild disease remote from term can be managed expectantly with very close supervision. Even in cases of severe disease remote from term, it may be appropriate to delay delivery to allow administration of corticosteroids to enhance fetal maturation. In general this should be undertaken in experienced medical centers with intense maternal and fetal monitoring.

The mainstay of intrapartum treatment of preeclampsia is magnesium sulfate for the prevention of seizures. ^[4]

Magnesium sulfate has minimal effect on maternal blood pressure and so other medications may be necessary to control maternal blood pressure before and during labor. It is best to avoid calcium channel blockers (e.g., nifedipine) as they may potentiate magnesium activity. Other choices include hydralazine, amlodipine, and nitroglycerine.

Women receiving magnesium therapy for preeclampsia require close monitoring of intake and output because oliguria can occur with severe disease and magnesium is renally excreted. Severe oliguria can be associated with increased serum magnesium levels and toxicity.

In labor, periodic assessment of maternal laboratory tests should be performed including:

• Complete blood count including platelets
• Serum transaminase levels

Some clinicians also follow

• Serum creatinine
• Fibrin degradation products
• Prothrombin time and partial thromboplastin time

Research

Women who had preeclampsia or eclampsia are more likely to suffer cardiac disease later in life, a risk factor often not appreciated by internists who may not tend to pay particular attention to pregnancy history. Several researchers, beginning with Chesley, ^[5] learned that women who had eclampsia in subsequent pregnancies were two to five times more likely to die of cardiac disease than women who did not have eclampsia. Sibai et. al. also found that women were more likely to develop chronic hypertension later in life if they had recurrent preeclampsia during pregnancy. ^[6] These studies are the basis for a statement by The National High Blood Pressure Education Program’s Working Group on High Blood Pressure During Pregnancy that asserts that recurrent hypertension in pregnancy, preeclampsia in a multipara, and early-onset disease in any pregnancy may all be a sign of increased future health risks.^[7]

Funai and colleagues described excess long-term mortality in women with prior preeclampsia, mainly due to a three-fold increase in deaths as a result of cardiovascular disease. ^[8]

These results have been confirmed by other investigators.^[9],^[10]

Another recent study by Karumanchi, attempting to find the cause of preeclampsia, found instead a likely reason women become ill. A substance called sFlit-1 (soluable fms-like tyrosine kinase-1) that is present in women with preeclampsia prevents new blood vessel formation, and if the placenta is impeded in its ability to invade the uterus, that may set the stage for preeclampsia. ^[11]

References

1. ↑ Chesley L. Hypertensive Disorders in Pregnancy. New York: Appleton-Century-Crofts; 1978.
2. ↑ Dieckman W. The Toxemias of Pregnancy, 2nd ed. St Louis: CV Mosby; 1952.
3. ↑ Chesley L. Hypertensive Disorders in Pregnancy. New York: Appleton-Century-Crofts; 1978.
4. ↑ Lucas MJ, Leveno KJ, Cunningham FG. A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. N Engl J Med 1995;333:201-5.
5. ↑ Chesley SC, Annitto JE, Cosgrove RA. The remote prognosis of eclamptic women. Sixth periodic report. Am J Obstet Gynecol 1976;124:446-59.
6. ↑ Sibai BM, el-Nazer A, Gonzalez-Ruiz A. Severe preeclampsia-eclampsia in young primigravid women: subsequent pregnancy outcome and remote prognosis. Am J Obstet Gynecol 1986;155:1011-6.
7. ↑ Gifford R, August P, Cunningham G, et al. The national high blood pressure education program working group on high blood pressure in pregnancy. Bethesda: National Institutes of Health and National Heart, Lung and Blood Institute; 2000.
8. ↑ Funai EF, Friedlander Y, Paltiel O, et al. Long-term mortality after preeclampsia. Epidemiology 2005;16:206-15.
9. ↑ McDonald SD, Malinowski A, Zhou Q, Yusuf S, Devereaux PJ. Cardiovascular sequelae of preeclampsia/eclampsia: a systematic review and meta-analyses. Am Heart J 2008;156:918-30.
10. ↑ Lykke JA Langhoff-Roos J, Sibai BM, Funai ER, Triche EW, Paidas MJ. Hypertensive pregnancy disorders and subsequent cardiovascular morbidity and type 2 diabetes mellitus in the mother. Hypertension 2009; 53(6):944-51.
11. ↑ Karumanchi SA, Bdolah Y. Hypoxia and sFlt-1 in preeclampsia: the "chicken-and-egg" question. Endocrinology 2004;145:4835-7.