PREECLAMPSIA

Preeclampsia, also referred to as toxemia, is a medical condition where hypertension arises in pregnancy (pregnancy-induced hypertension) in association with significant amounts of protein in the urine. It refers to a set of symptoms rather than any causative factor. Preeclampsia has been described as a disease of theories, because the cause is unknown. Preeclampsia is a condition that typically starts after the 20th week of pregnancy and is related to increased blood pressure and protein in the mother's urine (as a result of kidney problems). It is the most common of the dangerous pregnancy complications; it may affect both the mother and the unborn child. Pre-eclampsia affects the placenta, and it can affect the mother's kidney, liver, and brain. When preeclampsia causes seizures, the condition is known as eclampsia-the second leading cause of maternal death in the U.S. Preeclampsia is also a leading cause of fetal complications, which include low birth weight, premature birth, and stillbirth. Preeclampsia may develop from 20 weeks gestation (it is considered early onset before 32 weeks, which is associated with increased morbidity). Its progress differs among patients; most cases are diagnosed pre-term. Preeclampsia may also occur up to six weeks post-partum. Preeclampsia is classified into mild and severe. Preeclampsia is mild in 75% of cases and severe in 25% of them. In its extreme, the disease may lead to liver and renal failure, disseminated intravascular coagulopathy (DIC), and central nervous system (CNS) abnormalities. If preeclampsia-associated seizures develop, the disorder has developed into the condition called eclampsia. Mild preeclampsia is defined as the presence of hypertension (BP 140/90 mm Hg) on 2 occasions, at least 6 hours apart, but without evidence of end-organ damage in the patient.

Severe preeclampsia is defined as the presence of 1 of the following symptoms or signs in the presence of preeclampsia:

SBP of 160 mm Hg or higher or DBP of 110 mm Hg or higher on 2 occasions at least 6 hours apart

Proteinuria of more than 5 g in a 24-hour collection or more than 3+ on 2 random urine samples collected at least 4 hours apart

Pulmonary edema or cyanosis Oliguria (< 400 mL in 24 h) Persistent headaches Epigastric pain and/or impaired liver function Thrombocytopenia Oligohydramnios, decreased fetal growth, or placental abruption

Etiology
The etiology of preeclampsia is unknown but may be related to abnormal placentation.

Pathophysiology
Two Stage of the Pathophysiology of Preeclampsia
STAGE 1: Reduced Placental Perfusion abnormal implantation or vascular remodeling STAGE 2: Maternal Syndrome

WHAT LINKS STAGE 1 & 2?

ABNORMAL LIPID

STAGE 2

STAGE 1

METABOLISM

Reduced placental perfusion must interact with maternal factors to result in preeclampsia. Diverse manifestations are possible: maternal and fetal/placental factors may vary in proportion. In a woman with many predisposing factors, even a minor reduction in placental perfusion is sufficient for stage 2 to develop. In a woman with few predisposing factors, a profound reduction in placental perfusion may be required for preeclampsia to develop.

Predisposing factors

Reduced placental perfusion

Preeclampsia is characterized by metabolic abnormalities similar to those present in atherosclerosis: Hypertriglyceridemia Reduced HDL cholesterol Predominance of small-dense LDL cholesterol which have an increased potential to cause endothelial cell damage as compared to larger, more buoyant LDLs. In the presence of oxidative stress and inflammation, susceptible small-dense lipoproteins may be more easily oxidized, triggering Stage 2, maternal disease.

Stage 1

Abnormal lipid metabolism

Stage 2

+ Oxidative Stress .

+ Inflammation

There is growing evidence suggesting that preeclampsia may be an early manifestation of the metabolic syndrome: elevated triglyceride levels hyperinsulinemia insulin resistance relative glucose intolerance elevated blood pressure These factors have been linked to the development of preeclampsia. Studies have repeatedly demonstrated that metabolic abnormalities precede the clinical signs of preeclampsia: Insulin resistance and associated hyperinsulinemia Glucose intolerance Hypertriglyceridemia This suggests that insulin resistance and dyslipidemia may be factors involved in the development of preeclampsia. Similarities between the risk factors for preeclampsia and cardiovascular disease include: Insulin resistance

Dyslipidemia- decreased HDL levels and elevated triglyceride levels These risk factors are thought to play a causal role in the development of endothelial dysfunction, a characteristic feature of preeclampsia and cardiovascular disease.

Future implications:
Studies have demonstrated that women with a history of preeclampsia are at increased risk of developing cardiovascular disorders later in life. Women with preeclampsia who deliver preterm or with recurrent preeclampsia are at greatest risk. Women with preeclampsia have an approximate doubling of risk death from cardiovascular disease. These findings suggest that pregnancy may constitute a metabolic and vascular stress test which reveals a womans health in later life. Identification of maternal factors provides specific targets for prevention of preeclampsia in atrisk women.

Stage 1

INFLAMMATION

Stage 2

Preeclampsia is associated with an excessive inflammatory response compared with normal pregnancy. In a study done by Braekke, et.al (2005) inflammatory markers (calprotectin, CRP) were evaluated in maternal and fetal serum and amniotic fluid.

LABORATORY TESTS
Small studies have shown that random There currently is no single reliable, cost-effective screening test for preeclampsia. urinary protein-to-creatinine ratios predict the 24-hour urine total protein level and may provide a faster, simplified method of estimating proteinuria, providing that the protein values are less than 1 g in 24 hours. The urinary protein-to-creatinine ratio is not sensitive enough to differentiate mild and severe preeclampsia if significant proteinuria exists. However, a ratio of less than 0.2 effectively excludes the presence of significant proteinuria. A cutoff ratio of greater than 0.19 is a good predictor of significant proteinuria, with a sensitivity of 90 percent and a specificity of 70 percent. The negative predictive value of the urinary protein-to-creatinine ratio is 87 percent.

Risk Factors
Pregnancy-associated factors Chromosomal abnormalities Hydatidiform mole Hydrops fetalis Multifetal pregnancy Oocyte donation or donor insemination Structural congenital anomalies Urinary tract infection Maternal-specific factors Age greater than 35 years Age less than 20 years Black race Family history of preeclampsia Nulliparity Preeclampsia in a previous pregnancy Specific medical conditions: gestational diabetes, type I diabetes, obesity, chronic hypertension, renal disease, thrombophilias Stress Paternal-specific factors First-time father Previously fathered a preeclamptic pregnancy in another woman

Diagnosis
Though important manifestations of the disease, hypertension, proteinuria, and edema are not essential to the diagnosis of preeclampsia. The likelihood of preeclampsia increases when more elements of the disease are present.

Symptoms
headache visual disturbances epigastric or RUQ discomfort edema/rapid weight gain

Signs
hypertension retinal vasospasm hepatic tenderness facial and hand edema clonus

Fetal Effects
Preeclampsia has significant adverse fetal effects including decreased amniotic fluid levels, decreased fetal growth, placental abruption, and intrauterine fetal demise

What are other clinical effects of preeclampsia on the fetus? Change in fetal growth patterns What is the expected effect of preeclampsia on intrauterine fetal growth? (click on answer below) A. Small for gestational age B. Large for gestational age C. No effect

A. Small for Gestational Age Research has demonstrated that SGA infants are most commonly found in early onset preeclampsia (maternal clinical signs manifested before 37 weeks gestation). Two theories exist: Iatrogenic prematurity (maternal status mandates preterm delivery) Placental hypoperfusion related to impaired trophoblast invasion impairs fetal growth.

B. Large for Gestational Age Research has demonstrated that if the diagnosis of preeclampsia is made after 37 weeks of gestation, infants are of normal to LGA in size (especially in gestations of > 40 weeks). There may be a subset of preeclampsia without placental dysfunction. Or could fetal growth restriction be due to other factors? Stay tuned for further research!

Increase in maternal cardiac output late in pregnancy may be a compensatory mechanism in the presence of hypertension. The fetus can demand a greater share of the maternal circulation for survival and gets it! Treatment Delivery remains the ultimate treatment for preeclampsia. Although maternal and fetal risks must be weighed in determining the timing of delivery, clear indications for delivery exist. When possible, vaginal delivery is preferable to avoid the added physiologic stressors of cesarean delivery. If cesarean delivery must be used, regional anesthesia is preferred because it carries less maternal risk. In the presence of coagulopathy, use of regional anesthesia generally is contraindicated.

Antihypertensive Drugs Commonly Used in the Treatment of Severe Preeclampsia

Hydralazine (Apresoline)* Initial dose: 5 mg IV or 10 mg IM When blood pressure is controlled, repeat initial dose as needed (usually about every 3 hours; maximum, 400 mg per day). If blood pressure is not controlled in 20 minutes, repeat initial dose every 20 minutes until maximum dosage is reached, or go immediately to next step. If blood pressure is not controlled with a total of 20 mg IV or 30 mg IM, consider using a different antihypertensive drug (labetalol, nifedipine *Procardia+, sodium nitroprusside *Nitropress+).

Labetalol (Normodyne, Trandate)* Initial dose: 20 mg in IV bolus If blood pressure is not controlled, give 40 mg 10 minutes after initial dose and then 80 mg every 10 minutes for two additional doses (maximum: 220 mg). If blood pressure is not controlled, use a different antihypertensive drug (hydralazine, nifedipine, sodium nitroprusside).