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Pre-eclampsia, eclampsia or toxemia of pregnancy
Pre-eclampsia or preeclampsia (PE) is a disorder of pregnancy characterized by high blood pressure and a large amount of protein in the urine. The disorder usually occurs in the third trimester of pregnancy and gets worse over time. In severe disease there may be red blood cell breakdown, a low blood platelet count, impaired liver function, kidney dysfunction, swelling, shortness of breath due to fluid in the lungs, or visual disturbances. PE increases the risk of poor outcomes for both the mother and the baby. If left untreated, it may result in seizures at which point it is known as eclampsia.
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Toxemia of pregnancy is a severe condition that sometimes occurs in the latter weeks of pregnancy. It is characterized by high blood pressure; swelling of the hands, feet, and face; and an excessive amount of protein in the urine. If the condition is allowed to worsen, the mother may experience convulsions and coma, and the baby may be stillborn.
The term toxemia is actually a misnomer from the days when it was thought that the condition was caused by toxic (poisonous) substances in the blood. The illness is more accurately called preeclampsia before the convulsive stage and eclampsia afterward.
Preeclampsia affects between 2–8% of pregnancies worldwide. Hypertensive disorders of pregnancy are one of the most common causes of death due to pregnancy. They resulted in 29,000 deaths in 2013 – down from 37,000 deaths in 1990. Preeclampsia usually occurs after 32 weeks; however, if it occurs earlier it is associated with worse outcomes. Women who have had PE are at increased risk of heart disease later in life. The word eclampsia is from the Greek term for lightning. The first known description of the condition was by Hippocrates in the 5th century BCE
Swelling (especially in the hands and face) was originally considered an important sign for a diagnosis of preeclampsia. However, because swelling is a common occurrence in pregnancy, its utility as a distinguishing factor in preeclampsia is not great. Pitting edema (unusual swelling, particularly of the hands, feet, or face, notable by leaving an indentation when pressed on) can be significant, and should be reported to a health care provider.
In general, none of the signs of preeclampsia are specific, and even convulsions in pregnancy are more likely to have causes other than eclampsia in modern practice. Further, a symptom such as epigastric pain may be misinterpreted as heartburn. Diagnosis, therefore, depends on finding a coincidence of several preeclamptic features, the final proof being their regression after delivery.
The symptoms of toxemia of pregnancy (which may lead to death if not treated) are divided into three stages, each progressively more serious:
Mild preeclampsia symptoms include edema (puffiness under the skin due to fluid accumulation in the body tissues, often noted around the ankles), mild elevation of blood pressure, and the presence of small amounts of protein in the urine.
Severe preeclampsia symptoms include extreme edema, extreme elevation of blood pressure, the presence of large amounts of protein in the urine, headache, dizziness, double vision, nausea, vomiting, and severe pain in the right upper portion of the abdomen.
Eclampsia symptoms include convulsions and coma.
Known risk factors for preeclampsia include:
*Nulliparity (never given birth)
*Older age, and diabetes mellitus
*Prior history of preeclampsia
*Family history of preeclampsia
*Advanced maternal age (>35 years)
*Antiphospholipid antibody syndrome
*Having donated a kidney.
*Having sub-clinical hypothyroidism or thyroid antibodies
It is also more frequent in a women’s first pregnancy and if she is carrying twins. The underlying mechanism involves abnormal formation of blood vessels in the placenta amongst other factors. Most cases are diagnosed before delivery. Rarely, preeclampsia may begin in the period after delivery. While historically both high blood pressure and protein in the urine were required to make the diagnosis, some definitions also include those with hypertension and any associated organ dysfunction. Blood pressure is defined as high when it is greater than 140 mmHg systolic or 90 mmHg diastolic at two separate times, more than four hours apart in a women after twenty weeks of pregnancy. PE is routinely screened for during prenatal care.
There is no definitive known cause of preeclampsia, though it is likely related to a number of factors. Some of these factors include:
*Abnormal placentation (formation and development of the placenta)
*Prior or existing maternal pathology – preeclampsia is seen more at a higher incidence in individuals with preexisting hypertension, obesity, antiphospholipid antibody syndrome, and those with history of preeclampsia
*Dietary factors, e.g. calcium supplementation in areas where dietary calcium intake is low has been shown to reduce the risk of preeclampsia.
*Environmental factors, e.g. air pollution
*Those with long term high blood pressure have a risk 7 to 8 times higher than those without.
Physiologically, research has linked preeclampsia to the following physiologic changes: alterations in the interaction between the maternal immune response and the placenta, placental injury, endothelial cell injury, altered vascular reactivity, oxidative stress, imbalance among vasoactive substances, decreased intravascular volume, and disseminated intravascular coagulation.
While the exact cause of preeclampsia remains unclear, there is strong evidence that a major cause predisposing a susceptible woman to preeclampsia is an abnormally implanted placenta. This abnormally implanted placenta is thought to result in poor uterine and placental perfusion, yielding a state of hypoxia and increased oxidative stress and the release of anti-angiogenic proteins into the maternal plasma along with inflammatory mediators. A major consequence of this sequence of events is generalized endothelial dysfunction. The abnormal implantation is thought to stem from the maternal immune system’s response to the placenta and refers to evidence suggesting a lack of established immunological tolerance in pregnancy. Endothelial dysfunction results in hypertension and many of the other symptoms and complications associated with preclampsia.
One theory proposes that certain dietary deficiencies may be the cause of some cases. Also, there is the possibility that some forms of preeclampsia and eclampsia are the result of deficiency of blood flow in the uterus.
Pre-eclampsia is diagnosed when a pregnant woman develops:
*Blood pressure >_ 140 mm Hg systolic or >_ 90 mm Hg diastolic on two separate readings taken at least four to six hours apart after 20 weeks gestation in an individual with previously normal blood pressure.
*In a woman with essential hypertension beginning before 20 weeks gestational age, the diagnostic criteria are: an increase in systolic blood pressure (SBP) of >_ 30mmHg or an increase in diastolic blood pressure (DBP) of >_15mmHg.
*Proteinuria >_ 0.3 grams (300 mg) or more of protein in a 24-hour urine sample or a SPOT urinary protein to creatinine ratio >_ 0.3 or a urine dipstick reading of 1+ or greater (dipstick reading should only be used if other quantitative methods are not available)
Suspicion for preeclampsia should be maintained in any pregnancy complicated by elevated blood pressure, even in the absence of proteinuria. Ten percent of individuals with other signs and symptoms of preeclampsia and 20% of individuals diagnosed with eclampsia show no evidence of proteinuria. In the absence of proteinuria, the presence of new-onset hypertension (elevated blood pressure) and the new onset of one or more of the following is suggestive of the diagnosis of preeclampsia:
*Evidence of kidney dysfunction (oliguria, elevated creatinine levels)
*Impaired liver function (impaired liver function tests)
*Thrombocytopenia (platelet count <100,000/microliter)
*Ankle edema pitting type
*Cerebral or visual disturbances
*Preeclampsia is a progressive disorder and these signs of organ dysfunction are indicative of severe preeclampsia. A systolic blood pressure ?160 or diastolic blood pressure ?110 and/or proteinuria >5g in a 24-hour period is also indicative of severe preeclampsia. Clinically, individuals with severe preeclampsia may also present epigastric/right upper quadrant abdominal pain, headaches, and vomiting. Severe preeclampsia is a significant risk factor for intrauterine fetal death.
Of note, a rise in baseline blood pressure (BP) of 30 mmHg systolic or 15 mmHg diastolic, while not meeting the absolute criteria of 140/90, is still considered important to note, but is not considered diagnostic.
There have been many assessments of tests aimed at predicting preeclampsia, though no single biomarker is likely to be sufficiently predictive of the disorder. Predictive tests that have been assessed include those related to placental perfusion, vascular resistance, kidney dysfunction, endothelial dysfunction, and oxidative stress. Examples of notable tests include:
*Doppler ultrasonography of the uterine arteries to investigate for signs of inadequate placental perfusion. This test has a high negative predictive value among those individuals with a history of prior preeclampsia.
*Elevations in serum uric acid (hyperuricemia) is used by some to “define” preeclampsia, though it has been found to be a poor predictor of the disorder. Elevated levels in the blood (hyperuricemia) are likely due to reduced uric acid clearance secondary to impaired kidney function.
*Angiogenic proteins such as vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) and anti-angiogenic proteins such as soluble fms-like tyrosine kinase-1 (sFlt-1) have shown promise for potential clinical use in diagnosing preeclampsia, though evidence is sufficient to recommend a clinical use for these markers.
*Recent studies have shown that looking for podocytes, specialized cells of the kidney, in the urine has the potential to aid in the prediction of preeclampsia. Studies have demonstrated that finding podocytes in the urine may serve as an early marker of and diagnostic test for preeclampsia. Research is ongoing.
Pre-eclampsia can mimic and be confused with many other diseases, including chronic hypertension, chronic renal disease, primary seizure disorders, gallbladder and pancreatic disease, immune or thrombotic thrombocytopenic purpura, antiphospholipid syndrome and hemolytic-uremic syndrome. It must be considered a possibility in any pregnant woman beyond 20 weeks of gestation. It is particularly difficult to diagnose when preexisting disease such as hypertension is present. Women with acute fatty liver of pregnancy may also present with elevated blood pressure and protein in the urine, but differs by the extent of liver damage. Other disorders that can cause high blood pressure include thyrotoxicosis, pheochromocytoma, and drug misuse
Preeclampsia and eclampsia cannot be completely cured until the pregnancy is over. Until that time, treatment includes the control of high blood pressure and the intravenous administration of drugs to prevent convulsions. Drugs may also be given to stimulate the production of urine. In some severe cases, early delivery of the baby is needed to ensure the survival of the mother.
Recommendations for prevention include: aspirin in those at high risk, calcium supplementation in areas with low intake, and treatment of prior hypertension with medications. In those with PE delivery of the fetus and placenta is an effective treatment. When delivery becomes recommended depends on how severe the PE and how far along in pregnancy a person is. Blood pressure medication, such as labetalol and methyldopa, may be used to improve the mother’s condition before delivery. Magnesium sulfate may be used to prevent eclampsia in those with severe disease. Bedrest and salt intake have not been found to be useful for either treatment or prevention.
Protein or calorie supplementation have no effect on preeclampsia rates, and dietary protein restriction does not appear to increase preeclampsia rates. Further, there is no evidence that changing salt intake has an effect.
Supplementation with antioxidants such as vitamin C and E has no effect on preeclampsia incidence, nor does supplementation with vitamin D. Therefore, supplementation with vitamins C, E, and D is not recommended for reducing the risk of pre-eclampsia.
Calcium supplementation of at least 1 gram per day is recommended during pregnancy as it prevents preeclampsia where dietary calcium intake is low, especially for those at high risk. Low selenium status is associated with higher incidence of preeclampsia.
Taking aspirin is associated with a 1% to 5% reduction in preeclampsia and a 1% to 5% reduction in premature births in women at high risk. The WHO recommends low-dose aspirin for the prevention of preeclampsia in women at high risk and recommend it be started before 20 weeks of pregnancy. The United States Preventive Services Task Force recommends a low-dose regimen for women at high risk beginning in the 12th week.
There is insufficient evidence to recommend either exercise or strict bedrest as preventative measures of pre-eclampsia.
In low-risk pregnancies the association between cigarette smoking and a reduced risk of preeclampsia has been consistent and reproducible across epidemiologic studies. High-risk pregnancies (those with pregestational diabetes, chronic hypertension, history of preeclampsia in a previous pregnancy, or multifetal gestation) showed no significant protective effect. The reason for this discrepancy is not definitively known; research supports speculation that the underlying pathology increases the risk of preeclampsia to such a degree that any measurable reduction of risk due to smoking is masked. However, the damaging effects of smoking on overall health and pregnancy outcomes outweighs the benefits in decreasing the incidence of preeclampsia. It is recommended that smoking be stopped prior to, during and after pregnancy
Restriction of salt in the diet may help reduce swelling, it does not prevent the onset of high blood pressure or the appearance of protein in the urine. During prenatal visits, the doctor routinely checks the woman’s weight, blood pressure, and urine. If toxemia is detected early, complications may be reduced.